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<Chapter Language="En" OutputMedium="All" ID="b978-3-642-27728-3_114-1">
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<ChapterID>114-1</ChapterID>
<ChapterDOI>10.1007/978-3-642-27728-3_114-1</ChapterDOI>
<ChapterTitle Language="En">Stem Cells<!--<query ID="Q1"><query_paragraph>Please
confirm the chapter title.</query_paragraph></query>--></ChapterTitle>
<ChapterFirstPage>1</ChapterFirstPage>
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<ChapterCopyright>
<CopyrightHolderName>Springer-Verlag Berlin Heidelberg</CopyrightHolderName>
<CopyrightYear>2014</CopyrightYear>
</ChapterCopyright>
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<RegistrationDate>
<Year>2014</Year>
<Month>12</Month>
<Day>16</Day>
</RegistrationDate>
<Received>
<Year>2014</Year>
<Month>12</Month>
<Day>16</Day>
<Hour>12</Hour>
<Minute>31</Minute>
<Second>52</Second>
</Received>
<Accepted>
<Year>2014</Year>
<Month>12</Month>
<Day>16</Day>
<Hour>12</Hour>
<Minute>31</Minute>
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<ChapterContext>
<BookID>43401_0_En</BookID>
<BookTitle>Drug Discovery and Evaluation: Pharmacological Assays</BookTitle>
</ChapterContext>
</ChapterInfo>
<ChapterHeader>
<AuthorGroup>
<Author CorrespondingAffiliationID="Aff1" AffiliationIDS="Aff1" SpringerReferenc
eID="176797">
<AuthorName>
<GivenName>Benedikt</GivenName>
<FamilyName>Müller</FamilyName>
</AuthorName>
<Contact>
<Email>muellerb@hs-albsig.de</Email>
</Contact>
</Author>
<Author AffiliationIDS="Aff1" SpringerReferenceID="156829">
<AuthorName>
<GivenName>Suzanne</GivenName>
<FamilyName>Kadereit</FamilyName>
</AuthorName>
<Contact>
<Email>suzanne.kadereit@uni-konstanz.de</Email>
</Contact>
</Author>
<Affiliation ID="Aff1">
<OrgDivision>Faculty of Life Sciences</OrgDivision>
<OrgName>Albstadt-Sigmaringen University</OrgName>
<OrgAddress>
<City>Sigmaringen</City>
<Country>Germany</Country>
</OrgAddress>
</Affiliation>
</AuthorGroup>
<Abstract ID="Abs1" Language="En" OutputMedium="Online">
<Heading>Abstract</Heading>
<Para ID="Par1">In the last 20 years, costs of pharmaceuticals have grown faster
than other parts of health care, with estimated costs for drugs reaching market
ranging around 800 million USD (DiMasi et al. 2003). Accumulating data and nume
rous failed clinical trials indicates that drug development and evaluation on an
imal models, animal-derived in vitro test systems, and standard human cell lines
are not reliably predictive for human efficacy and safety (Perel et al. 2007; L
eist and Hartung 2013). Failed drugs increase the general costs of development,
particularly if failing in very late stages of development, as clinical trial te
sting is extremely expensive with phase III trials generating around 40 %
of overall drug development costs (Roy 2012). Failure in the clinical trial sta
ge can moreover result in unnecessary suffering due to unanticipated severe side
effects, even resulting in life-threatening situations such as in the case of t
esting of TGN1412 (Attarwala 2010). Also, failures such as in the case of Vioxx,
where cardiac toxicity emerged only with large-scale use in humans, are difficu
lt to predict with currently available methodologies (Karha and Topol 2004).</Pa
ra>
</Abstract>
</ChapterHeader>
<Body>
<Section1 Type="Introduction" ID="Sec1">
<Heading>Introduction</Heading>
<Para ID="Par2">In the last 20 years, costs of pharmaceuticals have grown faster
than other parts of health care, with estimated costs for drugs reaching market
ranging around 800 million USD (DiMasi et al. <CitationRef CitationID="CR29">20
03</CitationRef>). Accumulating data and numerous failed <IndexTerm>clinical tri
als<Primary>Clinical trials</Primary></IndexTerm> indicates that drug developmen
t and evaluation on animal models, animal-derived in vitro test systems, and sta
ndard human cell lines are not reliably predictive for human efficacy and safety
(Perel et al. <CitationRef CitationID="CR107">2007</CitationRef>; Leist and Har
tung <CitationRef CitationID="CR84">2013</CitationRef>). Failed drugs increase t
he general costs of development, particularly if failing in very late stages of
development, as clinical trial testing is extremely expensive with phase III tri
als generating around 40 % of overall drug development costs (Roy <Citati
onRef CitationID="CR118">2012</CitationRef>). Failure in the clinical trial stag
e can moreover result in unnecessary suffering due to unanticipated severe side
effects, even resulting in life-threatening situations such as in the case of te
sting of TGN1412 (Attarwala <CitationRef CitationID="CR6">2010</CitationRef>). A
lso, failures such as in the case of Vioxx, where cardiac toxicity emerged only
with large-scale use in humans, are difficult to predict with currently availabl
e methodologies (Karha and Topol <CitationRef CitationID="CR74">2004</CitationRe
f>).</Para>
<Para ID="Par3">Animal models and in vitro systems with animal cells have failed
repeatedly over the years, mainly due to differences in species-specific metabo
lism, neurogenesis, signaling, and immune function <!--<query ID="Q2"><query_par
agraph>Please check if “immune function” should be changed to 
01C;immuno-function.”</query_paragraph></query>-->(Dohnal et al. <Citatio
nRef CitationID="CR31">2014</CitationRef>; Hengstler et al. <CitationRef Citatio
nID="CR61">1999</CitationRef>; Lazarov and Marr <CitationRef CitationID="CR83">2
013</CitationRef>; Mestas and Hughes <CitationRef CitationID="CR96">2004</Citati
onRef>). Hepatotoxicity is the most frequent reason for withdrawal of already ap
proved drug, followed by hematologic and cardiac toxicity (Fung et al. <Citation
Ref CitationID="CR45">2001</CitationRef>). One of the most prominent examples of
failure of animal models to predict human toxicity was <IndexTerm>thalidomide<P
rimary>Thalidomide</Primary></IndexTerm>, which passed testing in two-species an
imal testing without any indication of teratogenicity, resulting in thousands of
humans born with severe developmental defects in extremity growth (Kim and Scia
lli <CitationRef CitationID="CR75">2011</CitationRef>). The only currently valid
ated in vitro test with stem cells, the <IndexTerm>embryonic stem cell test (EST
)<Primary>Embryonic stem cell test (EST)</Primary></IndexTerm>, also failed to d
etect the teratogenicity of thalidomide in its original format (zur Nieden et al
. <CitationRef CitationID="CR160">2004</CitationRef>). The validated EST is usin
g murine, not human, embryonic stem cells (Heuer et al. <CitationRef CitationID=
"CR62">1993</CitationRef>). When using more sophisticated endpoints or human emb
ryonic stem cells (hESCs), the predictivity of the EST is improved (discussed in
more detail later).</Para>
<Para ID="Par4">Development, particularly of the human brain, is likewise very s
pecies specific. The human brain is much more complex than other vertebrate brai
ns, with its development continuing past birth. Due to the complexity of its dev
elopment, the human brain is particularly sensitive to insults during developmen
t. Moreover, it was shown that some receptors that are important during <IndexTe
rm>brain development<Primary>Brain development</Primary></IndexTerm> are express
ed differently in human and rodent brains. For example, Gassmann and colleagues
investigated the role of the aryl hydrocarbon receptor (AhR) in persistent organ
ic pollutant (POP)-induced <IndexTerm>developmental neurotoxicity (DNT)<Primary>
Developmental neurotoxicity (DNT)</Primary></IndexTerm>. They found that in cont
rast to mouse neural progenitor cells that were susceptible to POP-induced DNT,
human neural progenitor cells were far less susceptible to DNT due to the absenc
e of AhR (Gassmann et al. <CitationRef CitationID="CR47">2010</CitationRef>). Th
us, toxicological pathways are difficult to model with sufficient predictability
in rodent systems.</Para>
<Para ID="Par5">One additional problem arising recently is <IndexTerm>REACH<Prim
ary>REACH</Primary></IndexTerm> (Registration, Evaluation, Authorization of Chem
icals), a new European Union legislation mandating that chemicals produced for,
or imported into, the European market are evaluated for their safety for humans
(Schoeters <CitationRef CitationID="CR121">2010</CitationRef>). The number of ch
emicals that need to be tested under REACH is daunting, with estimates reaching
over 100,000 chemicals, by far exceeding the numbers of available animals requir
ed for this evaluation. It is estimated that testing under REACH will use 20 tim
es more animals and cost 6 times as much as estimated during development of the
legislation. Currently, regulatory testing has neither the high-throughput metho
ds nor <IndexTerm>alternatives to animal testing<Primary>Alternatives to animal
testing</Primary></IndexTerm> to be able to comply under REACH (Hartung and Rovi
da <CitationRef CitationID="CR59">2009</CitationRef>).</Para>
<Para ID="Par6">Drug development and testing taking place in human cells is curr
ently performed on cell lines which are mostly derived from tumor tissues. Accor
dingly, apart from chromosomal anomalies, these cells also harbor defects in nor
mal regulatory pathways of cell cycle, cell death, and senescence and may be mor
e robust to toxicity than cells in vivo, rendering prediction of toxicity for no
rmal cells difficult. On the other hand, drug development and evaluation in norm
al human <IndexTerm>primary cells<Primary>Primary cells</Primary></IndexTerm> ar
e also not desirable; as such cells are associated with a far-too-high batch-tobatch variability. Moreover, human primary material is only scarcely available a
nd does not grow well (if at all) in culture and can certainly not supply the qu
antities of cell materials required to support high- to ultrahigh-throughput scr
eening in drug development, left alone mandatory testing under REACH. This also
holds true for tissue stem cells isolated from human fetal or adult tissue.</Par
a>
<Para ID="Par7">The derivation of <IndexTerm>human pluripotent stem cells (PSCs)
<Primary>Human pluripotent stem cells (PSCs)</Primary></IndexTerm>, which not on
ly are relatively normal but also grow indefinitely in culture and are able to g
enerate all cell types of the human body, has raised high hopes that such cells
could support the demands for the cell numbers needed for drug development and t
esting. Moreover, with such cells, <IndexTerm>human disease models<Primary>Human
disease models</Primary></IndexTerm> can be developed which will not only infor
m on mechanistic aspects of disease etiology but also enable a more targeted dev
elopment of drugs. It is anticipated that PSCs will in the near future replace c
lassical cell lines used in drug development and testing. Although classical cel
l lines are much easier and cheaper to culture, they do not allow for a more sop
histicated cell type-specific testing, as cell type choice is limited. Often, th
e cell type of standard, tumor-derived cell lines is also ill defined and does n
ot correspond to fully differentiated cells in vivo. Moreover, for the two main
target cell types of human drug toxicity, hepatocytes and cardiomyocytes, no ade
quate human cell lines exist.</Para>
<Para ID="Par8">For their better scalability to high throughput, possibility for
disease modeling, and thus applicability to drug development and evaluation, th
is chapter will focus on PSCs. In contrast to fetal and adult stem cells which c
an be grown only to a limited extent in culture, PSCs can generate large amounts
of progeny in culture and can still be differentiated into all cell types of th
e human body. Not only does this alleviate batch-to-batch variability considerab
ly, but PSCs can provide sufficient number of cells for high-throughput <IndexTe
rm>screening<Primary>High throughput screening</Primary></IndexTerm> of the thou
sands of compounds generated through combinatorial chemistry. They can also gene
rate meaningful disease models in which compounds can be screened for efficacy,
moreover with genotype specificity, and thus allow for personalized medicine. As
PSC-derived cell culture models can be (and are already partly) characterized a
s to their molecular underpinnings, they enable identification of target-selecti
ve compounds, as well as function-based approaches, where therapeutic effects ca
n be observed by normalizing a disease-specific abnormality.</Para>
</Section1>
<Section1 ID="Sec2">
<Heading>Pluripotent Stem Cell Properties</Heading>
<Para ID="Par9">Due to their promising properties, human pluripotent stem cells
(PSCs) have raised high hopes for both scientific and medical applications since
the first successful isolation of an <IndexTerm>embryonic stem cell<Primary>Emb
ryonic stem cell</Primary></IndexTerm> (hESC) line from human blastocysts in 199
8 (Thomson et al. <CitationRef CitationID="CR141">1998</CitationRef>). PSCs exhi
bit two unique properties in comparison to all other cells: pluripotency and lon
g-term self-renewal in culture. Pluripotency is the ability to generate cells fr
om all three germ layers (mesoderm, endoderm, and ectoderm) as well as cells of
the germ line, i.e., all cell types of the body (Gao et al. <CitationRef Citatio
nID="CR46">2013</CitationRef>). Hence, PSCs can be used to generate any human ti
ssue. Moreover, as the cells are self-renewing, meaning that they can divide ind
efinitely into identical daughter cells, these cells can be maintained in cultur
e for extended periods of time without losing their <IndexTerm>stem cell propert
ies<Primary>Stem cell properties</Primary></IndexTerm>. This enables culturing o
f PSCs over extended passages without loss of their potential to generate all ce
ll types of the body.</Para>
<Para ID="Par10">Importantly, and in contrast to most other cell lines, hESCs ar
e karyotypically normal and maintain this property for extended periods of cultu
re, if maintained properly (Englund et al. <CitationRef CitationID="CR37">2010</
CitationRef>; Wenger et al. <CitationRef CitationID="CR149">2004</CitationRef>).
Differences in the <IndexTerm>karyotype<Primary>Karyotype</Primary></IndexTerm>
of cancer cell lines were demonstrated to lead to high variation in gene expres
sion patterns, thus making it difficult to reproduce results even when using the
same cell line (Abdallah et al. <CitationRef CitationID="CR1">2013</CitationRef
>). In order to generate in vitro models as similar as possible to the in vivo s
ituation, a normal karyotype, as provided by hESCs, is essential.</Para>
<Para ID="Par11">In 2007, the so-called <IndexTerm>induced pluripotent stem cell
s<Primary>Induced pluripotent stem cells</Primary></IndexTerm> (hiPSCs) were gen
erated for the first time from human adult somatic cells, opening even further h
orizons (Takahashi et al. <CitationRef CitationID="CR139">2007</CitationRef>). T
o achieve this, the group of Yamanaka used transcription factors which were alre
ady known to regulate pluripotency in hESCs and influence cell proliferation and
differentiation: Oct4, Sox2, c-Myc, and Klf4 (Niwa et al. <CitationRef Citation
ID="CR103">2000</CitationRef>; Bullejos et al. <CitationRef CitationID="CR19">20
00</CitationRef>; Chen et al. <CitationRef CitationID="CR20">2003</CitationRef>;
Kanazawa et al. <CitationRef CitationID="CR73">2003</CitationRef>; Mitsui et al
. <CitationRef CitationID="CR97">2003</CitationRef>). The introduction of these
<IndexTerm>transcription factors<Primary>Transcription factors</Primary></IndexT
erm> into adult, terminally differentiated, fibroblasts induced the so-called re
programming of the somatic DNA in the fibroblasts and led to cells exhibiting pr
operties very similar to embryonic stem cells. During <IndexTerm>reprogramming<P
rimary>Reprogramming</Primary></IndexTerm>, epigenetic marks accumulated during
development and further maturation to terminally differentiated cells are stripp
ed off the DNA. At the same time, the DNA is reprogrammed to the pluripotent sta
te. The exact processes and mechanisms operating are still largely unknown and i
ncompletely understood. These induced PSCs expressed pluripotency gene expressio
n patterns, had an epigenetic profile similar to hESCs, and could differentiate
into cells of all three germ layers. Thus, by overexpressing only four <IndexTer
m>transcription factors<Primary>Transcription factors</Primary></IndexTerm> invo
lved in the maintenance of the pluripotent network, Yamanaka and colleagues succ
eeded in reprogramming somatic DNA to pluripotency. Since 2007, the approaches u
sed for <IndexTerm>reprogramming<Primary>Reprogramming</Primary></IndexTerm> of
human somatic cells to generate hiPSCs have become more robust and are steadily
being improved (Ma et al. <CitationRef CitationID="CR87">2013</CitationRef>; Dre
ws et al. <CitationRef CitationID="CR33">2012</CitationRef>).</Para>
<Para ID="Par12">The generation of hiPSCs caused widespread enthusiasm, as the u
se of iPSCs for cellular therapies offers a way to prevent immune rejections upo
n transplantation, by generating <IndexTerm>patient-specific hiPSCs<Primary>Pati
ent-specific hIPSCs</Primary></IndexTerm> from the patient’s own cells. S
uch cells can then be used to generate therapeutic cells that presumably would n
ot be rejected by the patient they have been derived from. However, it has also
emerged that not all hiPSC lines are truly pluripotent, likely due to incomplete
reprogramming of the somatic DNA. A<!--<query ID="Q3"><query_paragraph>Please c
heck if edit to sentence starting “A deeper look at the molecular level&#
x2026;” is okay.</query_paragraph></query>--> deeper look at the molecula
r level has furthermore revealed that hiPSC lines cluster together and separate
from hESC lines, when analyzing global gene expression and methylation patterns
(Kim et al. <CitationRef CitationID="CR76">2010</CitationRef>; Chin et al. <Cita
tionRef CitationID="CR22">2009</CitationRef>). Also, hiPSCs harbor a higher amou
nt of mutations than hESCs, some stemming from the original somatic cells, but m
any induced through the reprogramming process itself (Lister et al. <CitationRef
CitationID="CR86">2011</CitationRef>; Ji et al. <CitationRef CitationID="CR71">
2012</CitationRef>). Some of these mutations may be caused by the introduction o
f viral vectors into the genome during reprogramming and disruption of normal ge
nes or regulatory sequences. Additional <IndexTerm>mutations<Primary>Mutations</
Primary></IndexTerm> include point mutations, nonsense mutations, missense mutat
ions, splice variations, or copy number variations (Hussein et al. <CitationRef
drug testing, and predictive toxicology studies (Han et al. <CitationRef Citatio
nID="CR57">2011</CitationRef>; Gross et al. <CitationRef CitationID="CR56">2012<
/CitationRef>; Teoh and Cheong <CitationRef CitationID="CR140">2012</CitationRef
>). Patient-derived hiPSCs can also be used to generate disease models for clini
cal testing, an approach that will be discussed in more detail further down. An
additional advantage of hiPSCs is the avoidance of ethical <IndexTerm>issues<Pri
mary>Ethical issues, hiPSCs</Primary></IndexTerm> raised by the destruction of e
arly embryos to generate hESCs. This has caused research with hESCs to be strict
ly regulated or even completely prohibited in some countries (Teoh and Cheong <C
itationRef CitationID="CR140">2012</CitationRef>). The use of hiPSCs on the othe
r hand is far less regulated and can be carried out in any laboratory that is in
terested in this field, which led to a very large scientific community involved
in hiPSC research in a very short time.</Para>
<Para ID="Par16">The choice of the type of <IndexTerm>pluripotent stem cell<Prim
ary>Pluripotent stem cell</Primary><Secondary>choice of type of</Secondary></Ind
exTerm> (hESC vs. hiPSC) depends on the application in which they are going to b
e used. When developing a patient-specific approach or a disease model, iPSC tec
hnology enables the generation of cells with a particular disease background tha
t cannot always be recreated easily with ESCs. On the other hand, when generatin
g a developmental model or defined target cell types for transplantation, hESCs
are often preferred. Due to the genetic abnormalities discussed above for hiPSCs
, therapeutic cells generated from hESCs would presumably be of higher quality.<
/Para>
<Para ID="Par17">Murine ESCs can be used to faithfully recreate in vivo developm
ent in the dish (Barberi et al. <CitationRef CitationID="CR10">2003</CitationRef
>). Similar behavior is inferred for human ESCs, and accordingly, hESCs now serv
e to model early human development. For example, <IndexTerm>embryoid bodies (EBs
)<Primary>Embryoid bodies (EBs)</Primary></IndexTerm>, small aggregations of PSC
s differentiating in suspension, are used as a model of early embryogenesis as t
he differentiating cells generate spontaneously cells of all three germ layers (
Dvash et al. <CitationRef CitationID="CR34">2004</CitationRef>). EBs can also be
used for toxicological testing (Meganathan et al. <CitationRef CitationID="CR93
">2012</CitationRef>). As EBs can be guided toward specific cell lineages by exp
osure to specific growth factors, they are widely used as the initial step for d
irected differentiation and can be used for the generation of <IndexTerm>develop
mental models<Primary>Developmental models</Primary></IndexTerm> of specific cel
l lineages (Schuldiner et al. <CitationRef CitationID="CR122">2000</CitationRef>
). Cells of the neural cell lineage can be generated by adding growth factors su
ch as retinoic acid, nerve growth factor, or fibroblast growth factor 2 (Schuldi
ner et al. <CitationRef CitationID="CR123">2001</CitationRef>; Reubinoff et al.
<CitationRef CitationID="CR113">2001</CitationRef>). For directed differentiatio
n of human ESCs toward cardiomyocytes, a mix of <IndexTerm>growth factors<Primar
y>Growth factors</Primary></IndexTerm> such as bone morphogenetic protein 4, act
ivin A, and fibroblast growth factor 2 is needed (Murry and Keller <CitationRef
CitationID="CR102">2008</CitationRef>). An overview of growth factors needed to
generate specific cell types was generated by Williams and colleagues (Williams
et al. <CitationRef CitationID="CR150">2012</CitationRef>).</Para>
<Para ID="Par18">In combination, hESCs and hiPSCs are expected to offer an unlim
ited supply of human cells of desired type to generate in vitro models for devel
opmental studies, disease modeling, drug discovery, and development of personali
zed medicine approaches and offer sufficient human cell material for toxicology
and REACH.</Para>
</Section1>
<Section1 ID="Sec3">
<Heading>Human Versus Animal Models</Heading>
<Para ID="Par19">The major advantage of human PSCs is that they allow to generat
e human models. The value of animal models in correctly predicting the outcome o
f treatment strategies in humans is controversial (Perel et al. <CitationRef Cit
ationID="CR107">2007</CitationRef>). The large number of potential treatment mod
alities that were proven beneficial in animal studies but finally failed in rand
omized clinical trials can only partly be explained by shortcomings in the desig
n of animal studies, such as insufficient statistical power or overoptimistic co
nclusions about efficacy (van der Worp et al. <CitationRef CitationID="CR144">20
10</CitationRef>). More importantly, <IndexTerm>animal models<Primary>Animal mod
els</Primary></IndexTerm> can often times simply not predict human responses to
drugs (Inoue and Yamanaka <CitationRef CitationID="CR68">2011</CitationRef>). On
a genetic level, for example, inflammation-related changes in gene expression i
n mice were often very different from the changes observed in humans (Seok et al
. <CitationRef CitationID="CR129">2013</CitationRef>). Furthermore, as many gene
tic variants of <IndexTerm>human diseases<Primary>Human diseases</Primary></Inde
xTerm> are located in noncoding regions of the genome, which have no similarity
in other organisms, the introduction of these genetic variants into animal genom
es is unlikely to yield a disease phenotype (Merkle and Eggan <CitationRef Citat
ionID="CR95">2013</CitationRef>). Another example that is hard to replicate in a
nimal models is the impact of diseases on the proteome and its complex regulatio
n which often leads to secondary effects. In case of the neurodegenerative Alzhe
imer’s disease, for example, a toxic effect caused by protein misfolding
could not be recapitulated in a transgenic mouse model (Winklhofer et al. <Citat
ionRef CitationID="CR151">2008</CitationRef>).</Para>
<Para ID="Par20">Recently, a large-scale compound drug screen of neural stem cel
ls and rat mixed cortical neurons was performed (Malik et al. <CitationRef Citat
ionID="CR88">2014</CitationRef>). The researchers tested 2,000 compounds for the
ir species and cell type specificity. From these 2,000 substances, 100 were show
n to be specifically toxic for human neural stem cells. In a secondary screen wi
th different human neural cell types, they were able to demonstrate a cell typespecific <IndexTerm>toxicity<Primary>Cell-type specific toxicity</Primary></Inde
xTerm> for more than 80 % of these compounds. These results illustrate cl
early that drugs can have various effects on different cells, depending both on
the species and the target cell type, and that in order to predictably identify
compounds affecting human cells, human in vitro models are needed with, if possi
ble, the cell type of interest.</Para>
<Para ID="Par21">There have also been numerous cases in which drugs that were al
ready approved and commercially available had to be withdrawn from the market, a
fter successful preapproval trials. In these cases, animal models did not predic
t the harmful effects on humans, which were only reported in studies after the d
amage had already been done. Two widely known examples are the drugs <IndexTerm>
rofecoxib (Vioxx)<Primary>Rofecoxib (Vioxx)</Primary></IndexTerm> and <IndexTerm
>thalidomide (Contergan)<Primary>Thalidomide (Contergan)</Primary></IndexTerm>.
Rofecoxib (Vioxx) is a nonsteroidal anti-inflammatory drug (NSAID) inhibiting Co
x-2 that was approved in 1999 for the treatment of osteoarthritis, acute pain, a
nd primary dysmenorrhea (Roth-Cline <CitationRef CitationID="CR116">2006</Citati
onRef>). Shortly after approval, thrombotic side effects were postulated (Title
et al. <CitationRef CitationID="CR142">2003</CitationRef>), and in the following
years, several studies investigating other potential applications for rofecoxib
reported cardiac toxicity, particularly in long-term studies (Bombardier et al.
<CitationRef CitationID="CR14">2000</CitationRef>; Graham et al. <CitationRef C
itationID="CR54">2005</CitationRef>; Juni et al. <CitationRef CitationID="CR72">
2004</CitationRef>; Mukherjee et al. <CitationRef CitationID="CR100">2001</Citat
ionRef>). In 2004, the drug was finally withdrawn due to increased cardiovascula
r risk following long-term use. In this case, cardiac toxicity was only noticed
after long-term use and this in millions of users. Such effects are difficult to
detect in animal models and initial clinical trials due to small-size samples.
In case of thalidomide, the outcome was also severe as it caused malformation of
the limbs of around 10<!--<query ID="Q4"><query_paragraph>Please check if the c
hange of decimal dot to decimal comma is okay.</query_paragraph></query>-->,000
infants worldwide in the 1950s and 1960s. The drug was approved in Germany in 19
57 and used as a sedative or hypnotic. Later on, it was commonly used by pregnan
t women to alleviate morning sickness. It then emerged that thalidomide had tera
togenic effects during a very narrow time window of pregnancy, between 20 and 36
days postfertilization (Kim and Scialli <CitationRef CitationID="CR75">2011</Ci
n of the highly embryo and neurotoxic substance methylmercury, which had not bee
n successfully classified in the conventional EST previously, with cardiac endpo
int alone (Stummann et al. <CitationRef CitationID="CR137">2007</CitationRef>).
Hayess et al. have developed a test for determining DNT of substances by inducin
g neural differentiation of mouse ESCs. They were able to determine <IndexTerm>D
NT<Primary>DNT</Primary></IndexTerm> with a 100 % predictivity and accura
cy for nine substances (Hayess et al. <CitationRef CitationID="CR60">2013</Citat
ionRef>). Another endpoint that has been established successfully is testing for
the expression of three genes involved in <IndexTerm>osteogenesis<Primary>Osteo
genesis</Primary></IndexTerm>. The results of this osteoblast differentiation as
say (ESTo), testing 19 substances, showed a high correlation to results of the c
onventional EST and allowed for the detection of 2,3,7,8-tetra-chlorodibenzo-<Em
phasis Type="Italic">p</Emphasis>-dioxin (TCDD), an embryotoxic substance that c
ould not be detected otherwise (de Jong et al. <CitationRef CitationID="CR26">20
14</CitationRef>). These examples show the importance of a broad range of geneti
c markers for successfully identifying embryotoxic compounds.</Para>
<Para ID="Par41">Apart from endpoints based on gene expression, <IndexTerm>prote
in markers<Primary>Protein markers</Primary></IndexTerm> and metabolic activity
can potentially indicate embryotoxic properties. A proteomics approach carried o
ut by Osman and coworkers showed that EBs exposed to the embryotoxic monobutyl p
hthalate for 25 h showed a shift in the intracellular levels of 33 protei
ns, including cardiac markers and chromatin modulator enzymes (Osman et al. <Cit
ationRef CitationID="CR106">2010</CitationRef>). A recent study investigated the
impact of embryotoxic substances on genes of the <IndexTerm>energy metabolism<P
rimary>Energy metabolism</Primary></IndexTerm>. The transcriptomics approach of
van Dartel et al. revealed dynamic changes in energy metabolism during early ESC
differentiation in response to embryotoxic compounds. The test showed activatio
n of glycolysis, truncated activation of the tricarboxylic acid (TCA) cycle, act
ivation of lipid synthesis, and activation of glutaminolysis (van Dartel et al.
<CitationRef CitationID="CR143">2014</CitationRef>).</Para>
<Para ID="Par42">As outlined previously, the use of human cells has important ad
vantages compared to murine cells. <IndexTerm>Species-specific differences<Prima
ry>Species-specific differences</Primary></IndexTerm> in embryonic development b
etween man and mouse have been reported including DNA methylation, DNA repair, a
nd the expression of genes involved in drug metabolism (Krtolica et al. <Citatio
nRef CitationID="CR81">2009</CitationRef>). Accordingly, an EST using hESCs woul
d significantly enhance the validity as such species-specificity problems would
be alleviated (Wobus and Löser <CitationRef CitationID="CR152">2011</Cita
tionRef>). A recent study, adapting the EST to human cells, using hiPSCs and hum
an dermal fibroblasts has successfully detected the teratogenic effects of thali
domide, which is not detected in the validated mouse EST (Aikawa et al. <Citatio
nRef CitationID="CR5">2014</CitationRef>). Additional proof-of-concept studies w
ith the goal to determine the suitability of hESCs for toxicology tests have bee
n performed. Adler and coworkers carried out studies evaluating the effects of a
ll-trans retinoic acid and 13-cis retinoic acid on human ESCs, human ES-derived
progenitors, and human foreskin fibroblasts, thereby detecting a toxic effect of
13-cis retinoic acid, which was not detected in previous mouse EST analyses (Ad
ler et al. <CitationRef CitationID="CR2">2008a</CitationRef>). Moreover, in a se
cond study, they established a <IndexTerm>human EST<Primary>Human EST</Primary><
/IndexTerm> yielding results very similar to the mouse EST (Adler et al. <Citati
onRef CitationID="CR3">2008b</CitationRef>). They proposed to use additional mar
kers of undifferentiated ESCs as well as markers of neural plate morphogenesis a
nd early cardiogenesis to expand the amount of molecular endpoints for evaluatio
n of embryotoxicity.</Para>
<Para ID="Par43">As of today, the validation process of the EST is an ongoing pr
oject, and the test is continuously being improved by addition of new endpoints
and adjustments for high-throughput screening and the future use of hESCs or hiP
SCs. Although studies of an EST with human cells are very promising, still many
issues need to be addressed. These include insufficient sensitivity and specific
ity of the test. Importantly, test systems with hESCs or hiPSCs are plagued by p
</Body>
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PDFType="Typeset" OutputMedium="Online"/>
<ChapterBackmatter>
<Bibliography ID="Bib1">
<Heading>References<!--<query ID="Q7"><query_paragraph>Please cite Estevan et al
. and Kitaoka et al. in text.</query_paragraph></query>--></Heading>
<Citation ID="CR1">
<BibArticle>
<BibAuthorName>
<Initials>BY</Initials>
<FamilyName>Abdallah</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SD</Initials>
<FamilyName>Horne</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JB</Initials>
<FamilyName>Stevens</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Liu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AY</Initials>
<FamilyName>Ying</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Vanderhyden</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SA</Initials>
<FamilyName>Krawetz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Gorelick</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HH</Initials>
<FamilyName>Heng</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Single cell heterogeneity: why unstable genomes are
incompatible with average profiles</ArticleTitle>
<JournalTitle>Cell Cycle</JournalTitle>
<VolumeID>12</VolumeID>
<IssueID>23</IssueID>
<FirstPage>3640</FirstPage>
<LastPage>3649</LastPage>
<BibArticleDOI>10.4161/cc.26580</BibArticleDOI>
</BibArticle>
<BibUnstructured>Abdallah BY, Horne SD, Stevens JB, Liu G, Ying AY, Vanderhyden
B, Krawetz SA, Gorelick R, Heng HH (2013) Single cell heterogeneity: why unstabl
e genomes are incompatible with average profiles. Cell Cycle 12(23):3640–
3649. doi:10.4161/cc.26580</BibUnstructured>
</Citation>
<Citation ID="CR2">
<BibArticle>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Adler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Lindqvist</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Uddenberg</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hyllner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Strehl</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">Testing potential developmental toxicants with a cyt
otoxicity assay based on human embryonic stem cells</ArticleTitle>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>36</VolumeID>
<IssueID>2</IssueID>
<FirstPage>129</FirstPage>
<LastPage>140</LastPage>
</BibArticle>
<BibUnstructured>Adler S, Lindqvist J, Uddenberg K, Hyllner J, Strehl R (2008a)
Testing potential developmental toxicants with a cytotoxicity assay based on hum
an embryonic stem cells. Altern Lab Anim 36(2):129–140</BibUnstructured>
</Citation>
<Citation ID="CR3">
<BibArticle>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Adler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Pellizzer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Hareng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Hartung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">First steps in establishing a developmental toxicity
test method based on human embryonic stem cells</ArticleTitle>
<JournalTitle>Toxicol In Vitro</JournalTitle>
<VolumeID>22</VolumeID>
<IssueID>1</IssueID>
<FirstPage>200</FirstPage>
<LastPage>211</LastPage>
<BibArticleDOI>10.1016/j.tiv.2007.07.013</BibArticleDOI>
</BibArticle>
<BibUnstructured>Adler S, Pellizzer C, Hareng L, Hartung T, Bremer S (2008b) Fir
st steps in establishing a developmental toxicity test method based on human emb
ryonic stem cells. Toxicol In Vitro 22(1):200–211. doi:10.1016/j.tiv.2007
.07.013</BibUnstructured>
</Citation>
<Citation ID="CR4">
<BibArticle>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Agarwal</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Loh</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EM</Initials>
<FamilyName>McLoughlin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Huang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Park</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JD</Initials>
<FamilyName>Miller</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Huo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Okuka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RM</Initials>
<FamilyName>Dos Reis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Loewer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Ng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DL</Initials>
<FamilyName>Keefe</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FD</Initials>
<FamilyName>Goldman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AJ</Initials>
<FamilyName>Klingelhutz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Liu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Telomere elongation in induced pluripotent stem cell
s from dyskeratosis congenita patients</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>464</VolumeID>
<IssueID>7286</IssueID>
<FirstPage>292</FirstPage>
<LastPage>296</LastPage>
<BibArticleDOI>10.1038/nature08792</BibArticleDOI>
</BibArticle>
<BibUnstructured>Agarwal S, Loh Y, McLoughlin EM, Huang J, Park I, Miller JD, Hu
o H, Okuka M, Dos Reis RM, Loewer S, Ng H, Keefe DL, Goldman FD, Klingelhutz AJ,
Liu L, Daley GQ (2010) Telomere elongation in induced pluripotent stem cells fr
om dyskeratosis congenita patients. Nature 464(7286):292–296. doi:10.1038
/nature08792</BibUnstructured>
</Citation>
<Citation ID="CR5">
<BibArticle>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Aikawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Kunisato</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Nagao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Kusaka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Takaba</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Ohgami</FamilyName>
</BibAuthorName>
<Year>2014</Year>
<ArticleTitle Language="En">Detection of thalidomide embryotoxicity by in vitro
embryotoxicity testing based on human iPS cells</ArticleTitle>
<JournalTitle>J Pharmacol Sci</JournalTitle>
<VolumeID>124</VolumeID>
<IssueID>2</IssueID>
<FirstPage>201</FirstPage>
<LastPage>207</LastPage>
</BibArticle>
<BibUnstructured>Aikawa N, Kunisato A, Nagao K, Kusaka H, Takaba K, Ohgami K (20
14) Detection of thalidomide embryotoxicity by in vitro embryotoxicity testing b
ased on human iPS cells. J Pharmacol Sci 124(2):201–207</BibUnstructured>
</Citation>
<Citation ID="CR6">
<BibArticle>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Attarwala</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">TGN1412: from discovery to disaster</ArticleTitle>
<JournalTitle>J Young Pharm</JournalTitle>
<VolumeID>2</VolumeID>
<IssueID>3</IssueID>
<FirstPage>332</FirstPage>
<LastPage>336</LastPage>
<BibArticleDOI>10.4103/0975-1483.66810</BibArticleDOI>
</BibArticle>
<BibUnstructured>Attarwala H (2010) TGN1412: from discovery to disaster. J Young
Pharm 2(3):332–336. doi:10.4103/0975-1483.66810</BibUnstructured>
</Citation>
<Citation ID="CR7">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Balls</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Hellsten</FamilyName>
</BibAuthorName>
<Year>2002</Year>
<ArticleTitle Language="En">Statement of the scientific validity of the embryoni
c stem cell test (EST) – an in vitro test for embryotoxicity</ArticleTitl
e>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>30</VolumeID>
<IssueID>3</IssueID>
<FirstPage>265</FirstPage>
<LastPage>268</LastPage>
</BibArticle>
<BibUnstructured>Balls M, Hellsten E (2002) Statement of the scientific validity
of the embryonic stem cell test (EST) – an in vitro test for embryotoxic
ity. Altern Lab Anim 30(3):265–268</BibUnstructured>
</Citation>
<Citation ID="CR8">
<BibArticle>
<BibAuthorName>
<Initials>NV</Initials>
<FamilyName>Balmer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MK</Initials>
<FamilyName>Weng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Zimmer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>VN</Initials>
<FamilyName>Ivanova</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SM</Initials>
<FamilyName>Chambers</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Nikolaeva</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Jagtap</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Sachinidis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hescheler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Waldmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Leist</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Epigenetic changes and disturbed neural development
in a human embryonic stem cell-based model relating to the fetal valproate syndr
ome</ArticleTitle>
<JournalTitle>Hum Mol Genet</JournalTitle>
<VolumeID>21</VolumeID>
<IssueID>18</IssueID>
<FirstPage>4104</FirstPage>
<LastPage>4114</LastPage>
<BibArticleDOI>10.1093/hmg/dds239</BibArticleDOI>
</BibArticle>
<BibUnstructured>Balmer NV, Weng MK, Zimmer B, Ivanova VN, Chambers SM, Nikolaev
a E, Jagtap S, Sachinidis A, Hescheler J, Waldmann T, Leist M (2012) Epigenetic
changes and disturbed neural development in a human embryonic stem cell-based mo
del relating to the fetal valproate syndrome. Hum Mol Genet 21(18):4104–4
114. doi:10.1093/hmg/dds239</BibUnstructured>
</Citation>
<Citation ID="CR9">
<BibArticle>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Bantle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DJ</Initials>
<FamilyName>Fort</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JR</Initials>
<FamilyName>Rayburn</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DJ</Initials>
<FamilyName>DeYoung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SJ</Initials>
<FamilyName>Bush</FamilyName>
</BibAuthorName>
<Year>1990</Year>
<ArticleTitle Language="En">Further validation of FETAX: evaluation of the devel
opmental toxicity of five known mammalian teratogens and non-teratogens</Article
Title>
<JournalTitle>Drug Chem Toxicol</JournalTitle>
<VolumeID>13</VolumeID>
<IssueID>4</IssueID>
<FirstPage>267</FirstPage>
<LastPage>282</LastPage>
<BibArticleDOI>10.3109/01480549009032286</BibArticleDOI>
</BibArticle>
<BibUnstructured>Bantle JA, Fort DJ, Rayburn JR, DeYoung DJ, Bush SJ (1990) Furt
her validation of FETAX: evaluation of the developmental toxicity of five known
mammalian teratogens and non-teratogens. Drug Chem Toxicol 13(4):267–282.
doi:10.3109/01480549009032286</BibUnstructured>
</Citation>
<Citation ID="CR10">
<BibArticle>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Barberi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Klivenyi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NY</Initials>
<FamilyName>Calingasan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Lee</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Kawamata</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Loonam</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AL</Initials>
<FamilyName>Perrier</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Bruses</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>ME</Initials>
<FamilyName>Rubio</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Topf</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Tabar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NL</Initials>
<FamilyName>Harrison</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MF</Initials>
<FamilyName>Beal</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MA</Initials>
<FamilyName>Moore</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Studer</FamilyName>
</BibAuthorName>
<Year>2003</Year>
<ArticleTitle Language="En">Neural subtype specification of fertilization and nu
clear transfer embryonic stem cells and application in parkinsonian mice</Articl
eTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>21</VolumeID>
<IssueID>10</IssueID>
<FirstPage>1200</FirstPage>
<LastPage>1207</LastPage>
<BibArticleDOI>10.1038/nbt870</BibArticleDOI>
</BibArticle>
<BibUnstructured>Barberi T, Klivenyi P, Calingasan NY, Lee H, Kawamata H, Loonam
K, Perrier AL, Bruses J, Rubio ME, Topf N, Tabar V, Harrison NL, Beal MF, Moore
MA, Studer L (2003) Neural subtype specification of fertilization and nuclear t
ransfer embryonic stem cells and application in parkinsonian mice. Nat Biotechno
l 21(10):1200–1207. doi:10.1038/nbt870</BibUnstructured>
</Citation>
<Citation ID="CR11">
<BibArticle>
<BibAuthorName>
<Initials>LFZ</Initials>
<FamilyName>Batista</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MF</Initials>
<FamilyName>Pech</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FL</Initials>
<FamilyName>Zhong</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HN</Initials>
<FamilyName>Nguyen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KT</Initials>
<FamilyName>Xie</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AJ</Initials>
<FamilyName>Zaug</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SM</Initials>
<FamilyName>Crary</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Choi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Sebastiano</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Cherry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Giri</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Wernig</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BP</Initials>
<FamilyName>Alter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TR</Initials>
<FamilyName>Cech</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SA</Initials>
<FamilyName>Savage</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RA</Initials>
<FamilyName>Reijo Pera</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SE</Initials>
<FamilyName>Artandi</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Telomere shortening and loss of self-renewal in dysk
eratosis congenita induced pluripotent stem cells</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>474</VolumeID>
<IssueID>7351</IssueID>
<FirstPage>399</FirstPage>
<LastPage>402</LastPage>
<BibArticleDOI>10.1038/nature10084</BibArticleDOI>
</BibArticle>
<BibUnstructured>Batista LFZ, Pech MF, Zhong FL, Nguyen HN, Xie KT, Zaug AJ, Cra
ry SM, Choi J, Sebastiano V, Cherry A, Giri N, Wernig M, Alter BP, Cech TR, Sava
ge SA, Reijo Pera RA, Artandi SE (2011) Telomere shortening and loss of self-ren
ewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474(7351):
399–402. doi:10.1038/nature10084</BibUnstructured>
</Citation>
<Citation ID="CR12">
<BibArticle>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Bayart</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Cohen-Haguenauer</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Technological overview of iPS induction from human a
dult somatic cells</ArticleTitle>
<JournalTitle>Curr Gene Ther</JournalTitle>
<VolumeID>13</VolumeID>
<IssueID>2</IssueID>
<FirstPage>73</FirstPage>
<LastPage>92</LastPage>
</BibArticle>
<BibUnstructured>Bayart E, Cohen-Haguenauer O (2013) Technological overview of i
PS induction from human adult somatic cells. Curr Gene Ther 13(2):73–92</
BibUnstructured>
</Citation>
<Citation ID="CR13">
<BibArticle>
<BibAuthorName>
<Initials>U</Initials>
<FamilyName>Ben-David</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Benvenisty</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">The tumorigenicity of human embryonic and induced pl
uripotent stem cells</ArticleTitle>
<JournalTitle>Nat Rev Cancer</JournalTitle>
<VolumeID>11</VolumeID>
<IssueID>4</IssueID>
<FirstPage>268</FirstPage>
<LastPage>277</LastPage>
<BibArticleDOI>10.1038/nrc3034</BibArticleDOI>
</BibArticle>
<BibUnstructured>Ben-David U, Benvenisty N (2011) The tumorigenicity of human em
bryonic and induced pluripotent stem cells. Nat Rev Cancer 11(4):268–277.
doi:10.1038/nrc3034</BibUnstructured>
</Citation>
<Citation ID="CR14">
<BibArticle>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Bombardier</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Laine</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Reicin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Shapiro</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Burgos-Vargas</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Davis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Day</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MB</Initials>
<FamilyName>Ferraz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CJ</Initials>
<FamilyName>Hawkey</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MC</Initials>
<FamilyName>Hochberg</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TK</Initials>
<FamilyName>Kvien</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TJ</Initials>
<FamilyName>Schnitzer</FamilyName>
</BibAuthorName>
<Year>2000</Year>
<ArticleTitle Language="En">Comparison of upper gastrointestinal toxicity of rof
ecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group</Ar
ticleTitle>
<JournalTitle>N Engl J Med</JournalTitle>
<VolumeID>343</VolumeID>
<IssueID>21</IssueID>
<FirstPage>1520</FirstPage>
<LastPage>1528, 2 p following 1528</LastPage>
<BibComments>0.1056/NEJM200011233432103</BibComments>
</BibArticle>
<BibUnstructured>Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Da
vis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ (2000) C
omparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patien
ts with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343(21):1520ȁ
3;1528, 2 p following 1528, 0.1056/NEJM200011233432103</BibUnstructured>
</Citation>
<Citation ID="CR15">
<BibArticle>
<BibAuthorName>
<Initials>SL</Initials>
<FamilyName>Boulet</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CA</Initials>
<FamilyName>Boyle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LA</Initials>
<FamilyName>Schieve</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Health care use and health and functional impact of
developmental disabilities among US children, 1997–2005</ArticleTitle>
<JournalTitle>Arch Pediatr Adolesc Med</JournalTitle>
<VolumeID>163</VolumeID>
<IssueID>1</IssueID>
<FirstPage>19</FirstPage>
<LastPage>26</LastPage>
<BibArticleDOI>10.1001/archpediatrics.2008.506</BibArticleDOI>
</BibArticle>
<BibUnstructured>Boulet SL, Boyle CA, Schieve LA (2009) Health care use and heal
th and functional impact of developmental disabilities among US children, 1997&#
x2013;2005. Arch Pediatr Adolesc Med 163(1):19–26. doi:10.1001/archpediat
rics.2008.506</BibUnstructured>
</Citation>
<Citation ID="CR16">
<BibArticle>
<BibAuthorName>
<Initials>GL</Initials>
<FamilyName>Boulting</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Kiskinis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GF</Initials>
<FamilyName>Croft</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MW</Initials>
<FamilyName>Amoroso</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DH</Initials>
<FamilyName>Oakley</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BJ</Initials>
<FamilyName>Wainger</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DJ</Initials>
<FamilyName>Williams</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DJ</Initials>
<FamilyName>Kahler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Yamaki</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Davidow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CT</Initials>
<FamilyName>Rodolfa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JT</Initials>
<FamilyName>Dimos</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Mikkilineni</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AB</Initials>
<FamilyName>MacDermott</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CJ</Initials>
<FamilyName>Woolf</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CE</Initials>
<FamilyName>Henderson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Wichterle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">A functionally characterized test set of human induc
ibUnstructured>
</Citation>
<Citation ID="CR18">
<BibArticle>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Buesen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Genschow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Slawik</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Visan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Luch</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Seiler</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Embryonic stem cell test remastered: comparison betw
een the validated EST and the new molecular FACS-EST for assessing developmental
toxicity in vitro</ArticleTitle>
<JournalTitle>Toxicol Sci</JournalTitle>
<VolumeID>108</VolumeID>
<IssueID>2</IssueID>
<FirstPage>389</FirstPage>
<LastPage>400</LastPage>
<BibArticleDOI>10.1093/toxsci/kfp012</BibArticleDOI>
</BibArticle>
<BibUnstructured>Buesen R, Genschow E, Slawik B, Visan A, Spielmann H, Luch A, S
eiler A (2009) Embryonic stem cell test remastered: comparison between the valid
ated EST and the new molecular FACS-EST for assessing developmental toxicity in
vitro. Toxicol Sci 108(2):389–400. doi:10.1093/toxsci/kfp012</BibUnstruct
ured>
</Citation>
<Citation ID="CR19">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Bullejos</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Diaz de la Guardia</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Barragan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Sanchez</FamilyName>
</BibAuthorName>
<Year>2000</Year>
<ArticleTitle Language="En">HMG-box sequences from microbats homologous to the h
uman SOX30 HMG-box</ArticleTitle>
<JournalTitle>Genetica</JournalTitle>
<VolumeID>110</VolumeID>
<IssueID>2</IssueID>
<FirstPage>157</FirstPage>
<LastPage>162</LastPage>
</BibArticle>
<BibUnstructured>Bullejos M, Diaz de la Guardia R, Barragan MJ, Sanchez A (2000)
HMG-box sequences from microbats homologous to the human SOX30 HMG-box. Genetic
a 110(2):157–162</BibUnstructured>
</Citation>
<Citation ID="CR20">
<BibArticle>
<BibAuthorName>
<Initials>X</Initials>
<FamilyName>Chen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EM</Initials>
<FamilyName>Whitney</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SY</Initials>
<FamilyName>Gao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>VW</Initials>
<FamilyName>Yang</FamilyName>
</BibAuthorName>
<Year>2003</Year>
<ArticleTitle Language="En">Transcriptional profiling of Kruppel-like factor 4 r
eveals a function in cell cycle regulation and epithelial differentiation</Artic
leTitle>
<JournalTitle>J Mol Biol</JournalTitle>
<VolumeID>326</VolumeID>
<IssueID>3</IssueID>
<FirstPage>665</FirstPage>
<LastPage>677</LastPage>
</BibArticle>
<BibUnstructured>Chen X, Whitney EM, Gao SY, Yang VW (2003) Transcriptional prof
iling of Kruppel-like factor 4 reveals a function in cell cycle regulation and e
pithelial differentiation. J Mol Biol 326(3):665–677</BibUnstructured>
</Citation>
<Citation ID="CR21">
<BibArticle>
<BibAuthorName>
<Initials>ABC</Initials>
<FamilyName>Cherry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Reprogramming cellular identity for regenerative med
icine</ArticleTitle>
<JournalTitle>Cell</JournalTitle>
<VolumeID>148</VolumeID>
<IssueID>6</IssueID>
<FirstPage>1110</FirstPage>
<LastPage>1122</LastPage>
<BibArticleDOI>10.1016/j.cell.2012.02.031</BibArticleDOI>
</BibArticle>
<BibUnstructured>Cherry ABC, Daley GQ (2012) Reprogramming cellular identity for
regenerative medicine. Cell 148(6):1110–1122. doi:10.1016/j.cell.2012.02
.031</BibUnstructured>
</Citation>
<Citation ID="CR22">
<BibArticle>
<BibAuthorName>
<Initials>MH</Initials>
<FamilyName>Chin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Mason</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Xie</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Volinia</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Singer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Peterson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Ambartsumyan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Aimiuwu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Richter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Khvorostov</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Ott</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Grunstein</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Lavon</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Benvenisty</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CM</Initials>
<FamilyName>Croce</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AT</Initials>
<FamilyName>Clark</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Baxter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AD</Initials>
<FamilyName>Pyle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MA</Initials>
<FamilyName>Teitell</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Pelegrini</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Plath</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>WE</Initials>
<FamilyName>Lowry</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Induced pluripotent stem cells and embryonic stem ce
lls are distinguished by gene expression signatures</ArticleTitle>
<JournalTitle>Cell Stem Cell</JournalTitle>
<VolumeID>5</VolumeID>
<IssueID>1</IssueID>
<FirstPage>111</FirstPage>
<LastPage>123</LastPage>
<BibArticleDOI>10.1016/j.stem.2009.06.008</BibArticleDOI>
</BibArticle>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Lazzari</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Characterisation of a neural teratogenicity assay ba
sed on human ESCs differentiation following exposure to valproic acid</ArticleTi
tle>
<JournalTitle>Curr Med Chem</JournalTitle>
<VolumeID>19</VolumeID>
<IssueID>35</IssueID>
<FirstPage>6065</FirstPage>
<LastPage>6071</LastPage>
</BibArticle>
<BibUnstructured>Colleoni S, Galli C, Gaspar JA, Meganathan K, Jagtap S, Heschel
er J, Sachinidis A, Lazzari G (2012) Characterisation of a neural teratogenicity
assay based on human ESCs differentiation following exposure to valproic acid.
Curr Med Chem 19(35):6065–6071</BibUnstructured>
</Citation>
<Citation ID="CR25">
<BibArticle>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Conti</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Cattaneo</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Neural stem cell systems: physiological players or i
n vitro entities?</ArticleTitle>
<JournalTitle>Nat Rev Neurosci</JournalTitle>
<VolumeID>11</VolumeID>
<IssueID>3</IssueID>
<FirstPage>176</FirstPage>
<LastPage>187</LastPage>
<BibArticleDOI>10.1038/nrn2761</BibArticleDOI>
</BibArticle>
<BibUnstructured>Conti L, Cattaneo E (2010) Neural stem cell systems: physiologi
cal players or in vitro entities? Nat Rev Neurosci 11(3):176–187. doi:10.
1038/nrn2761</BibUnstructured>
</Citation>
<Citation ID="CR26">
<BibArticle>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Jong</FamilyName>
<Particle>de</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Beek</FamilyName>
<Particle>van</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>AH</Initials>
<FamilyName>Piersma</FamilyName>
</BibAuthorName>
<Year>2014</Year>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Hochedlinger</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Thomson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Wang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Gao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Targeted bisulfite sequencing reveals changes in DNA
methylation associated with nuclear reprogramming</ArticleTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>27</VolumeID>
<IssueID>4</IssueID>
<FirstPage>353</FirstPage>
<LastPage>360</LastPage>
<BibArticleDOI>10.1038/nbt.1530</BibArticleDOI>
</BibArticle>
<BibUnstructured>Deng J, Shoemaker R, Xie B, Gore A, LeProust EM, Antosiewicz-Bo
urget J, Egli D, Maherali N, Park I, Yu J, Daley GQ, Eggan K, Hochedlinger K, Th
omson J, Wang W, Gao Y, Zhang K (2009) Targeted bisulfite sequencing reveals cha
nges in DNA methylation associated with nuclear reprogramming. Nat Biotechnol 27
(4):353–360. doi:10.1038/nbt.1530</BibUnstructured>
</Citation>
<Citation ID="CR28">
<BibArticle>
<BibAuthorName>
<Initials>FP</Initials>
<FamilyName>Di Giorgio</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GL</Initials>
<FamilyName>Boulting</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bobrowicz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KC</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">Human embryonic stem cell-derived motor neurons are
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Mitsumoto</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Chung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GF</Initials>
<FamilyName>Croft</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Saphier</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Leibel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Goland</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Wichterle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CE</Initials>
<FamilyName>Henderson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">Induced pluripotent stem cells generated from patien
ts with ALS can be differentiated into motor neurons</ArticleTitle>
<JournalTitle>Science</JournalTitle>
<VolumeID>321</VolumeID>
<IssueID>5893</IssueID>
<FirstPage>1218</FirstPage>
<LastPage>1221</LastPage>
<BibArticleDOI>10.1126/science.1158799</BibArticleDOI>
</BibArticle>
<BibUnstructured>Dimos JT, Rodolfa KT, Niakan KK, Weisenthal LM, Mitsumoto H, Ch
ung W, Croft GF, Saphier G, Leibel R, Goland R, Wichterle H, Henderson CE, Eggan
K (2008) Induced pluripotent stem cells generated from patients with ALS can be
differentiated into motor neurons. Science 321(5893):1218–1221. doi:10.1
126/science.1158799</BibUnstructured>
</Citation>
<Citation ID="CR31">
<BibArticle>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Dohnal</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Q</Initials>
<FamilyName>Wu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Kuča</FamilyName>
</BibAuthorName>
<Year>2014</Year>
<ArticleTitle Language="En">Metabolism of aflatoxins: key enzymes and interindiv
idual as well as interspecies differences</ArticleTitle>
<JournalTitle>Arch Toxicol</JournalTitle>
<VolumeID>88</VolumeID>
<IssueID>9</IssueID>
<FirstPage>1635</FirstPage>
<LastPage>1644</LastPage>
<BibArticleDOI>10.1007/s00204-014-1312-9</BibArticleDOI>
</BibArticle>
<BibUnstructured>Dohnal V, Wu Q, Kuča K (2014) Metabolism of aflatoxins:
key enzymes and interindividual as well as interspecies differences. Arch Toxico
l 88(9):1635–1644. doi:10.1007/s00204-014-1312-9</BibUnstructured>
</Citation>
<Citation ID="CR32">
<BibArticle>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Doi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Park</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Wen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Murakami</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Aryee</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Irizarry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Herb</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Ladd-Acosta</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Rho</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Loewer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Miller</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Schlaeger</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AP</Initials>
<FamilyName>Feinberg</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Differential methylation of tissue- and cancer-speci
fic CpG island shores distinguishes human induced pluripotent stem cells, embryo
nic stem cells and fibroblasts</ArticleTitle>
<JournalTitle>Nat Genet</JournalTitle>
<VolumeID>41</VolumeID>
<IssueID>12</IssueID>
<FirstPage>1350</FirstPage>
<LastPage>1353</LastPage>
<BibArticleDOI>10.1038/ng.471</BibArticleDOI>
</BibArticle>
<BibUnstructured>Doi A, Park I, Wen B, Murakami P, Aryee MJ, Irizarry R, Herb B,
Ladd-Acosta C, Rho J, Loewer S, Miller J, Schlaeger T, Daley GQ, Feinberg AP (2
009) Differential methylation of tissue- and cancer-specific CpG island shores d
istinguishes human induced pluripotent stem cells, embryonic stem cells and fibr
oblasts. Nat Genet 41(12):1350–1353. doi:10.1038/ng.471</BibUnstructured>
</Citation>
<Citation ID="CR33">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Drews</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Jozefczuk</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Prigione</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Adjaye</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Human induced pluripotent stem cells – from m
echanisms to clinical applications</ArticleTitle>
<JournalTitle>J Mol Med (Berl)</JournalTitle>
<VolumeID>90</VolumeID>
<IssueID>7</IssueID>
<FirstPage>735</FirstPage>
<LastPage>745</LastPage>
<BibArticleDOI>10.1007/s00109-012-0913-0</BibArticleDOI>
</BibArticle>
<BibUnstructured>Drews K, Jozefczuk J, Prigione A, Adjaye J (2012) Human induced
pluripotent stem cells – from mechanisms to clinical applications. J Mol
Med (Berl) 90(7):735–745. doi:10.1007/s00109-012-0913-0</BibUnstructured
>
</Citation>
<Citation ID="CR34">
<BibArticle>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Dvash</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Mayshar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Darr</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>McElhaney</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Barker</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Yanuka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KJ</Initials>
<FamilyName>Kotkow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LL</Initials>
<FamilyName>Rubin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Benvenisty</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Eiges</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Temporal gene expression during differentiation of h
uman embryonic stem cells and embryoid bodies</ArticleTitle>
<JournalTitle>Hum Reprod</JournalTitle>
<VolumeID>19</VolumeID>
<IssueID>12</IssueID>
<FirstPage>2875</FirstPage>
<LastPage>2883</LastPage>
<BibArticleDOI>10.1093/humrep/deh529</BibArticleDOI>
</BibArticle>
<VolumeID>46</VolumeID>
<IssueID>3–4</IssueID>
<FirstPage>217</FirstPage>
<LastPage>230</LastPage>
<BibArticleDOI>10.1007/s11626-010-9289-z</BibArticleDOI>
</BibArticle>
<BibUnstructured>Englund MCO, Caisander G, Noaksson K, Emanuelsson K, Lundin K,
Bergh C, Hansson C, Semb H, Strehl R, Hyllner J (2010) The establishment of 20 d
ifferent human embryonic stem cell lines and subclones; a report on derivation,
culture, characterisation and banking. In Vitro Cell Dev Biol Anim 46(3–4
):217–230. doi:10.1007/s11626-010-9289-z</BibUnstructured>
</Citation>
<Citation ID="CR38">
<BibUnstructured>ESAC (2002) The use of scientifically-validated in vitro tests
for embryotoxicity. <ExternalRef><RefSource>http://ecvam.jrc.ec.europa.eu/</RefS
ource><RefTarget TargetType="URL" Address="http://ecvam.jrc.ec.europa.eu/"/></Ex
ternalRef>. Accessed 8 Dec 2014</BibUnstructured>
</Citation>
<Citation ID="CR39">
<BibUnstructured><!--<query ID="Q8"><query_paragraph>Please provide complete bib
liography details for Estevan et al. and Kitaoka et al.</query_paragraph></query
>-->Estevan C, Romero AC, Pamies D, Vilanova E, Sogorb MA Embryonic stem cells i
n toxicological studies. In: Embryonic stem cells – fefve</BibUnstructure
d>
</Citation>
<Citation ID="CR40">
<BibArticle>
<BibAuthorName>
<Initials>Q</Initials>
<FamilyName>Feng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Lu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Klimanskaya</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Gomes</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Kim</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Chung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GR</Initials>
<FamilyName>Honig</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Kim</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Lanza</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Hemangioblastic derivatives from human induced pluri
potent stem cells exhibit limited expansion and early senescence</ArticleTitle>
<JournalTitle>Stem Cells</JournalTitle>
<VolumeID>28</VolumeID>
<IssueID>4</IssueID>
<FirstPage>704</FirstPage>
<LastPage>712</LastPage>
<BibArticleDOI>10.1002/stem.321</BibArticleDOI>
</BibArticle>
<BibUnstructured>Feng Q, Lu S, Klimanskaya I, Gomes I, Kim D, Chung Y, Honig GR,
Kim K, Lanza R (2010) Hemangioblastic derivatives from human induced pluripoten
t stem cells exhibit limited expansion and early senescence. Stem Cells 28(4):70
4–712. doi:10.1002/stem.321</BibUnstructured>
</Citation>
<Citation ID="CR41">
<BibArticle>
<BibAuthorName>
<Initials>OP</Initials>
<FamilyName>Flint</FamilyName>
</BibAuthorName>
<Year>1993</Year>
<ArticleTitle Language="En">In vitro tests for teratogens: desirable endpoints,
test batteries and current status of the micromass teratogen test</ArticleTitle>
<JournalTitle>Reprod Toxicol</JournalTitle>
<VolumeID>7</VolumeID>
<IssueID>Suppl 1</IssueID>
<FirstPage>103</FirstPage>
<LastPage>111</LastPage>
</BibArticle>
<BibUnstructured>Flint OP (1993) In vitro tests for teratogens: desirable endpoi
nts, test batteries and current status of the micromass teratogen test. Reprod T
oxicol 7(Suppl 1):103–111</BibUnstructured>
</Citation>
<Citation ID="CR42">
<BibArticle>
<BibAuthorName>
<Initials>CE</Initials>
<FamilyName>Forristal</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KL</Initials>
<FamilyName>Wright</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NA</Initials>
<FamilyName>Hanley</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>ROC</Initials>
<FamilyName>Oreffo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FD</Initials>
<FamilyName>Houghton</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<FamilyName>Fratta</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EB</Initials>
<FamilyName>Sigg</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Maiorana</FamilyName>
</BibAuthorName>
<Year>1965</Year>
<ArticleTitle Language="En">Teratogenic effects of thalidomide in rabbits, rats,
hamsters, and mice</ArticleTitle>
<JournalTitle>Toxicol Appl Pharmacol</JournalTitle>
<VolumeID>7</VolumeID>
<FirstPage>268</FirstPage>
<LastPage>286</LastPage>
</BibArticle>
<BibUnstructured>Fratta ID, Sigg EB, Maiorana K (1965) Teratogenic effects of th
alidomide in rabbits, rats, hamsters, and mice. Toxicol Appl Pharmacol 7:268
013;286</BibUnstructured>
</Citation>
<Citation ID="CR45">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Fung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Thornton</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Mybeck</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JH</Initials>
<FamilyName>Wu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Hornbuckle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Muniz</FamilyName>
</BibAuthorName>
<Year>2001</Year>
<ArticleTitle Language="En">Evaluation of the characteristics of safety withdraw
al of prescription drugs from worldwide pharmaceutical markets-1960 to 1999</Art
icleTitle>
<JournalTitle>Ther Innov Regul Sci</JournalTitle>
<VolumeID>35</VolumeID>
<IssueID>1</IssueID>
<FirstPage>293</FirstPage>
<LastPage>317</LastPage>
<BibArticleDOI>10.1177/009286150103500134</BibArticleDOI>
</BibArticle>
<BibUnstructured>Fung M, Thornton A, Mybeck K, Wu JH, Hornbuckle K, Muniz E (200
<FamilyName>Rockel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Schreiber</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Fritsche</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Species-specific differential AhR expression protect
s human neural progenitor cells against developmental neurotoxicity of PAHs</Art
icleTitle>
<JournalTitle>Environ Health Perspect</JournalTitle>
<VolumeID>118</VolumeID>
<IssueID>11</IssueID>
<FirstPage>1571</FirstPage>
<LastPage>1577</LastPage>
<BibArticleDOI>10.1289/ehp.0901545</BibArticleDOI>
</BibArticle>
<BibUnstructured>Gassmann K, Abel J, Bothe H, Haarmann-Stemmann T, Merk HF, Quas
thoff KN, Rockel TD, Schreiber T, Fritsche E (2010) Species-specific differentia
l AhR expression protects human neural progenitor cells against developmental ne
urotoxicity of PAHs. Environ Health Perspect 118(11):1571–1577. doi:10.12
89/ehp.0901545</BibUnstructured>
</Citation>
<Citation ID="CR48">
<BibArticle>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Genschow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Scholz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Brown</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Piersma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Brady</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Clemann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Huuskonen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Paillard</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Becker</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<Year>2000</Year>
<ArticleTitle Language="En">Development of prediction models for three in vitro
embryotoxicity tests in an ECVAM validation study</ArticleTitle>
<JournalTitle>In Vitr Mol Toxicol</JournalTitle>
<VolumeID>13</VolumeID>
<IssueID>1</IssueID>
<FirstPage>51</FirstPage>
<LastPage>66</LastPage>
</BibArticle>
<BibUnstructured>Genschow E, Scholz G, Brown N, Piersma A, Brady M, Clemann N, H
uuskonen H, Paillard F, Bremer S, Becker K, Spielmann H (2000) Development of pr
ediction models for three in vitro embryotoxicity tests in an ECVAM validation s
tudy. In Vitr Mol Toxicol 13(1):51–66</BibUnstructured>
</Citation>
<Citation ID="CR49">
<BibArticle>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Genschow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Scholz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Seiler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Brown</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Piersma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Brady</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Clemann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Huuskonen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Paillard</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Becker</FamilyName>
</BibAuthorName>
<Year>2002</Year>
<ArticleTitle Language="En">The ECVAM international validation study on in vitro
embryotoxicity tests: results of the definitive phase and evaluation of predict
ion models. European Centre for the Validation of Alternative Methods</ArticleTi
tle>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>30</VolumeID>
<IssueID>2</IssueID>
<FirstPage>151</FirstPage>
<LastPage>176</LastPage>
</BibArticle>
<BibUnstructured>Genschow E, Spielmann H, Scholz G, Seiler A, Brown N, Piersma A
, Brady M, Clemann N, Huuskonen H, Paillard F, Bremer S, Becker K (2002) The ECV
AM international validation study on in vitro embryotoxicity tests: results of t
he definitive phase and evaluation of prediction models. European Centre for the
Validation of Alternative Methods. Altern Lab Anim 30(2):151–176</BibUns
tructured>
</Citation>
<Citation ID="CR50">
<BibArticle>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Genschow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Scholz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Pohl</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Seiler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Clemann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Becker</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Validation of the embryonic stem cell test in the in
ternational ECVAM validation study on three in vitro embryotoxicity tests</Artic
leTitle>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>32</VolumeID>
<IssueID>3</IssueID>
<FirstPage>209</FirstPage>
<LastPage>244</LastPage>
</BibArticle>
<BibUnstructured>Genschow E, Spielmann H, Scholz G, Pohl I, Seiler A, Clemann N,
Bremer S, Becker K (2004) Validation of the embryonic stem cell test in the int
ernational ECVAM validation study on three in vitro embryotoxicity tests. Altern
Lab Anim 32(3):209–244</BibUnstructured>
</Citation>
<Citation ID="CR51">
<BibArticle>
<BibAuthorName>
<Initials>Z</Initials>
<FamilyName>Ghosh</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KD</Initials>
<FamilyName>Wilson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Wu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Hu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Quertermous</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JC</Initials>
<FamilyName>Wu</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Persistent donor cell gene expression among human in
duced pluripotent stem cells contributes to differences with human embryonic ste
m cells</ArticleTitle>
<JournalTitle>PLoS One</JournalTitle>
<VolumeID>5</VolumeID>
<IssueID>2</IssueID>
<FirstPage>e8975</FirstPage>
<BibArticleDOI>10.1371/journal.pone.0008975</BibArticleDOI>
</BibArticle>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Loh</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PD</Initials>
<FamilyName>Manos</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Montserrat</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AD</Initials>
<FamilyName>Panopoulos</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Ruiz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>ML</Initials>
<FamilyName>Wilbert</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Yu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EF</Initials>
<FamilyName>Kirkness</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JCI</Initials>
<FamilyName>Belmonte</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DJ</Initials>
<FamilyName>Rossi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Thomson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LSB</Initials>
<FamilyName>Goldstein</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Somatic coding mutations in human induced pluripoten
t stem cells</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>471</VolumeID>
<IssueID>7336</IssueID>
<FirstPage>63</FirstPage>
<LastPage>67</LastPage>
<BibArticleDOI>10.1038/nature09805</BibArticleDOI>
</BibArticle>
<BibUnstructured>Gore A, Li Z, Fung H, Young JE, Agarwal S, Antosiewicz-Bourget
J, Canto I, Giorgetti A, Israel MA, Kiskinis E, Lee J, Loh Y, Manos PD, Montserr
at N, Panopoulos AD, Ruiz S, Wilbert ML, Yu J, Kirkness EF, Belmonte JCI, Rossi
DJ, Thomson JA, Eggan K, Daley GQ, Goldstein LSB, Zhang K (2011) Somatic coding
mutations in human induced pluripotent stem cells. Nature 471(7336):63–67
. doi:10.1038/nature09805</BibUnstructured>
</Citation>
<Citation ID="CR54">
<BibArticle>
<BibAuthorName>
<Initials>DJ</Initials>
<FamilyName>Graham</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Campen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Hui</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Spence</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Cheetham</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Levy</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Shoor</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>WA</Initials>
<FamilyName>Ray</FamilyName>
</BibAuthorName>
<Year>2005</Year>
<ArticleTitle Language="En">Risk of acute myocardial infarction and sudden cardi
ac death in patients treated with cyclo-oxygenase 2 selective and non-selective
non-steroidal anti-inflammatory drugs: nested case-control study</ArticleTitle>
<JournalTitle>Lancet</JournalTitle>
<VolumeID>365</VolumeID>
<IssueID>9458</IssueID>
<FirstPage>475</FirstPage>
<LastPage>481</LastPage>
<BibArticleDOI>10.1016/S0140-6736(05)17864-7</BibArticleDOI>
</BibArticle>
<BibUnstructured>Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, Shoor
S, Ray WA (2005) Risk of acute myocardial infarction and sudden cardiac death i
n patients treated with cyclo-oxygenase 2 selective and non-selective non-steroi
dal anti-inflammatory drugs: nested case-control study. Lancet 365(9458):475
013;481. doi:10.1016/S0140-6736(05)17864-7</BibUnstructured>
</Citation>
<Citation ID="CR55">
<BibArticle>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Grandjean</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PJ</Initials>
<FamilyName>Landrigan</FamilyName>
</BibAuthorName>
<Year>2006</Year>
<ArticleTitle Language="En">Developmental neurotoxicity of industrial chemicals<
/ArticleTitle>
<JournalTitle>Lancet</JournalTitle>
<VolumeID>368</VolumeID>
<IssueID>9553</IssueID>
<FirstPage>2167</FirstPage>
<LastPage>2178</LastPage>
<BibArticleDOI>10.1016/S0140-6736(06)69665-7</BibArticleDOI>
</BibArticle>
<BibUnstructured>Grandjean P, Landrigan PJ (2006) Developmental neurotoxicity of
industrial chemicals. Lancet 368(9553):2167–2178. doi:10.1016/S0140-6736
(06)69665-7</BibUnstructured>
</Citation>
<Citation ID="CR56">
<BibArticle>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Gross</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Pittermann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Reinhardt</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Cantz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Klusmann</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Prospects and challenges of reprogrammed cells in he
matology and oncology</ArticleTitle>
<JournalTitle>Pediatr Hematol Oncol</JournalTitle>
<VolumeID>29</VolumeID>
<IssueID>6</IssueID>
<FirstPage>507</FirstPage>
<LastPage>528</LastPage>
<BibArticleDOI>10.3109/08880018.2012.708707</BibArticleDOI>
</BibArticle>
<BibUnstructured>Gross B, Pittermann E, Reinhardt D, Cantz T, Klusmann J (2012)
Prospects and challenges of reprogrammed cells in hematology and oncology. Pedia
tr Hematol Oncol 29(6):507–528. doi:10.3109/08880018.2012.708707</BibUnst
ructured>
</Citation>
<Citation ID="CR57">
<BibArticle>
<BibAuthorName>
<Initials>SSW</Initials>
<FamilyName>Han</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LA</Initials>
<FamilyName>Williams</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KC</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Constructing and deconstructing stem cell models of
neurological disease</ArticleTitle>
<JournalTitle>Neuron</JournalTitle>
<VolumeID>70</VolumeID>
<IssueID>4</IssueID>
<FirstPage>626</FirstPage>
<LastPage>644</LastPage>
<BibArticleDOI>10.1016/j.neuron.2011.05.003</BibArticleDOI>
</BibArticle>
<BibUnstructured>Han SSW, Williams LA, Eggan KC (2011) Constructing and deconstr
ucting stem cell models of neurological disease. Neuron 70(4):626–644. do
i:10.1016/j.neuron.2011.05.003</BibUnstructured>
</Citation>
<Citation ID="CR58">
<BibArticle>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Hareng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Pellizzer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Schwarz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Hartung</FamilyName>
</BibAuthorName>
<Year>2005</Year>
<ArticleTitle Language="En">The integrated project ReProTect: a novel approach i
n reproductive toxicity hazard assessment</ArticleTitle>
<JournalTitle>Reprod Toxicol</JournalTitle>
<VolumeID>20</VolumeID>
<IssueID>3</IssueID>
<FirstPage>441</FirstPage>
<LastPage>452</LastPage>
<BibArticleDOI>10.1016/j.reprotox.2005.04.003</BibArticleDOI>
</BibArticle>
<BibUnstructured>Hareng L, Pellizzer C, Bremer S, Schwarz M, Hartung T (2005) Th
e integrated project ReProTect: a novel approach in reproductive toxicity hazard
assessment. Reprod Toxicol 20(3):441–452. doi:10.1016/j.reprotox.2005.04
.003</BibUnstructured>
</Citation>
<Citation ID="CR59">
<BibArticle>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Hartung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Rovida</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Chemical regulators have overreached</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>460</VolumeID>
<IssueID>7259</IssueID>
<FirstPage>1080</FirstPage>
<LastPage>1081</LastPage>
<BibArticleDOI>10.1038/4601080a</BibArticleDOI>
</BibArticle>
<BibUnstructured>Hartung T, Rovida C (2009) Chemical regulators have overreached
. Nature 460(7259):1080–1081. doi:10.1038/4601080a</BibUnstructured>
</Citation>
<Citation ID="CR60">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Hayess</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Riebeling</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Pirow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Steinfath</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Sittner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Slawik</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Luch</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AEM</Initials>
<FamilyName>Seiler</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">The DNT-EST: a predictive embryonic stem cell-based
assay for developmental neurotoxicity testing in vitro</ArticleTitle>
<JournalTitle>Toxicology</JournalTitle>
<VolumeID>314</VolumeID>
<IssueID>1</IssueID>
<FirstPage>135</FirstPage>
<LastPage>147</LastPage>
<BibArticleDOI>10.1016/j.tox.2013.09.012</BibArticleDOI>
</BibArticle>
<BibUnstructured>Hayess K, Riebeling C, Pirow R, Steinfath M, Sittner D, Slawik
B, Luch A, Seiler AEM (2013) The DNT-EST: a predictive embryonic stem cell-based
assay for developmental neurotoxicity testing in vitro. Toxicology 314(1):135&#
x2013;147. doi:10.1016/j.tox.2013.09.012</BibUnstructured>
</Citation>
<Citation ID="CR61">
<BibArticle>
<BibAuthorName>
<Initials>JG</Initials>
<FamilyName>Hengstler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Burg</FamilyName>
<Particle>Van der</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Steinberg</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Oesch</FamilyName>
</BibAuthorName>
<Year>1999</Year>
<ArticleTitle Language="En">Interspecies differences in cancer susceptibility an
d toxicity</ArticleTitle>
<JournalTitle>Drug Metab Rev</JournalTitle>
<VolumeID>31</VolumeID>
<IssueID>4</IssueID>
<FirstPage>917</FirstPage>
<LastPage>970</LastPage>
<BibArticleDOI>10.1081/DMR-100101946</BibArticleDOI>
</BibArticle>
<BibUnstructured>Hengstler JG, Van der Burg B, Steinberg P, Oesch F (1999) Inter
species differences in cancer susceptibility and toxicity. Drug Metab Rev 31(4):
917–970. doi:10.1081/DMR-100101946</BibUnstructured>
</Citation>
<Citation ID="CR62">
<BibArticle>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Heuer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Pohl</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<Year>1993</Year>
<ArticleTitle Language="En">Development of an in vitro embryotoxicity test using
murine embryonic stem cell cultures</ArticleTitle>
<JournalTitle>Toxicol In Vitro</JournalTitle>
<VolumeID>7</VolumeID>
<IssueID>4</IssueID>
<FirstPage>551</FirstPage>
<LastPage>556</LastPage>
<BibArticleDOI>10.1016/0887-2333(93)90064-C</BibArticleDOI>
</BibArticle>
<BibUnstructured>Heuer J, Bremer S, Pohl I, Spielmann H (1993) Development of an
in vitro embryotoxicity test using murine embryonic stem cell cultures. Toxicol
In Vitro 7(4):551–556. doi:10.1016/0887-2333(93)90064-C</BibUnstructured
>
</Citation>
<Citation ID="CR63">
<BibArticle>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Hockemeyer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Soldner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Beard</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Q</Initials>
<FamilyName>Gao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Mitalipova</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RC</Initials>
<FamilyName>DeKelver</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GE</Initials>
<FamilyName>Katibah</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Amora</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EA</Initials>
<FamilyName>Boydston</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Zeitler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>X</Initials>
<FamilyName>Meng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JC</Initials>
<FamilyName>Miller</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EJ</Initials>
<FamilyName>Rebar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PD</Initials>
<FamilyName>Gregory</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FD</Initials>
<FamilyName>Urnov</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Jaenisch</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Efficient targeting of expressed and silent genes in
human ESCs and iPSCs using zinc-finger nucleases</ArticleTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>27</VolumeID>
<IssueID>9</IssueID>
<FirstPage>851</FirstPage>
<LastPage>857</LastPage>
<BibArticleDOI>10.1038/nbt.1562</BibArticleDOI>
</BibArticle>
<BibUnstructured>Hockemeyer D, Soldner F, Beard C, Gao Q, Mitalipova M, DeKelver
RC, Katibah GE, Amora R, Boydston EA, Zeitler B, Meng X, Miller JC, Zhang L, Re
bar EJ, Gregory PD, Urnov FD, Jaenisch R (2009) Efficient targeting of expressed
and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biote
chnol 27(9):851–857. doi:10.1038/nbt.1562</BibUnstructured>
</Citation>
<Citation ID="CR64">
<BibArticle>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Hoelting</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Scheinhardt</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Bondarenko</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Schildknecht</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Kapitza</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Tanavde</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Tan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>QY</Initials>
<FamilyName>Lee</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Mecking</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Leist</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Kadereit</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">A 3-dimensional human embryonic stem cell (hESC)-der
ived model to detect developmental neurotoxicity of nanoparticles</ArticleTitle>
<JournalTitle>Arch Toxicol</JournalTitle>
<VolumeID>87</VolumeID>
<IssueID>4</IssueID>
<FirstPage>721</FirstPage>
<LastPage>733</LastPage>
<BibArticleDOI>10.1007/s00204-012-0984-2</BibArticleDOI>
</BibArticle>
<BibUnstructured>Hoelting L, Scheinhardt B, Bondarenko O, Schildknecht S, Kapitz
a M, Tanavde V, Tan B, Lee QY, Mecking S, Leist M, Kadereit S (2013) A 3-dimensi
onal human embryonic stem cell (hESC)-derived model to detect developmental neur
otoxicity of nanoparticles. Arch Toxicol 87(4):721–733. doi:10.1007/s0020
4-012-0984-2</BibUnstructured>
</Citation>
<Citation ID="CR65">
<BibArticle>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Höfer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Gerner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>U</Initials>
<FamilyName>Gundert-Remy</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Liebsch</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Schulte</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Vogel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Wettig</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Animal testing and alternative approaches for the hu
man health risk assessment under the proposed new European chemicals regulation<
/ArticleTitle>
<JournalTitle>Arch Toxicol</JournalTitle>
<VolumeID>78</VolumeID>
<IssueID>10</IssueID>
<FirstPage>549</FirstPage>
<LastPage>564</LastPage>
<BibArticleDOI>10.1007/s00204-004-0577-9</BibArticleDOI>
</BibArticle>
<BibUnstructured>Höfer T, Gerner I, Gundert-Remy U, Liebsch M, Schulte A,
Spielmann H, Vogel R, Wettig K (2004) Animal testing and alternative approaches
for the human health risk assessment under the proposed new European chemicals
regulation. Arch Toxicol 78(10):549–564. doi:10.1007/s00204-004-0577-9</B
ibUnstructured>
</Citation>
<Citation ID="CR66">
<BibArticle>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Hu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JP</Initials>
<FamilyName>Weick</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Yu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Ma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>X</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Thomson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Neural differentiation of human induced pluripotent
stem cells follows developmental principles but with variable potency</ArticleTi
tle>
<JournalTitle>Proc Natl Acad Sci U S A</JournalTitle>
<VolumeID>107</VolumeID>
<IssueID>9</IssueID>
<FirstPage>4335</FirstPage>
<LastPage>4340</LastPage>
<BibArticleDOI>10.1073/pnas.0910012107</BibArticleDOI>
</BibArticle>
<BibUnstructured>Hu B, Weick JP, Yu J, Ma L, Zhang X, Thomson JA, Zhang S (2010)
Neural differentiation of human induced pluripotent stem cells follows developm
ental principles but with variable potency. Proc Natl Acad Sci U S A 107(9):4335
–4340. doi:10.1073/pnas.0910012107</BibUnstructured>
</Citation>
<Citation ID="CR67">
<BibArticle>
<BibAuthorName>
<Initials>SM</Initials>
<FamilyName>Hussein</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NN</Initials>
<FamilyName>Batada</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Vuoristo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RW</Initials>
<FamilyName>Ching</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Autio</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Narva</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Ng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Sourour</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Hamalainen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Olsson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Lundin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Mikkola</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Trokovic</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Peitz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Brustle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DP</Initials>
<FamilyName>Bazett-Jones</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Alitalo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Lahesmaa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Nagy</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Otonkoski</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<JournalTitle>EMBO J</JournalTitle>
<VolumeID>33</VolumeID>
<IssueID>5</IssueID>
<FirstPage>409</FirstPage>
<LastPage>417</LastPage>
<BibArticleDOI>10.1002/embj.201387098</BibArticleDOI>
</BibArticle>
<BibUnstructured>Inoue H, Nagata N, Kurokawa H, Yamanaka S (2014) iPS cells: a g
ame changer for future medicine. EMBO J 33(5):409–417. doi:10.1002/embj.2
01387098</BibUnstructured>
</Citation>
<Citation ID="CR70">
<BibArticle>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Jelinek</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Peterka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Z</Initials>
<FamilyName>Rychter</FamilyName>
</BibAuthorName>
<Year>1985</Year>
<ArticleTitle Language="En">Chick embryotoxicity screening test – 130 sub
stances tested</ArticleTitle>
<JournalTitle>Indian J Exp Biol</JournalTitle>
<VolumeID>23</VolumeID>
<IssueID>10</IssueID>
<FirstPage>588</FirstPage>
<LastPage>595</LastPage>
</BibArticle>
<BibUnstructured>Jelinek R, Peterka M, Rychter Z (1985) Chick embryotoxicity scr
eening test – 130 substances tested. Indian J Exp Biol 23(10):588–
595</BibUnstructured>
</Citation>
<Citation ID="CR71">
<BibArticle>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Ji</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SH</Initials>
<FamilyName>Ng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Sharma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Neculai</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Hussein</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Sam</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Q</Initials>
<FamilyName>Trinh</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GM</Initials>
<FamilyName>Church</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JD</Initials>
<FamilyName>McPherson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Nagy</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NN</Initials>
<FamilyName>Batada</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Elevated coding mutation rate during the reprogrammi
ng of human somatic cells into induced pluripotent stem cells</ArticleTitle>
<JournalTitle>Stem Cells</JournalTitle>
<VolumeID>30</VolumeID>
<IssueID>3</IssueID>
<FirstPage>435</FirstPage>
<LastPage>440</LastPage>
<BibArticleDOI>10.1002/stem.1011</BibArticleDOI>
</BibArticle>
<BibUnstructured>Ji J, Ng SH, Sharma V, Neculai D, Hussein S, Sam M, Trinh Q, Ch
urch GM, McPherson JD, Nagy A, Batada NN (2012) Elevated coding mutation rate du
ring the reprogramming of human somatic cells into induced pluripotent stem cell
s. Stem Cells 30(3):435–440. doi:10.1002/stem.1011</BibUnstructured>
</Citation>
<Citation ID="CR72">
<BibArticle>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Juni</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Nartey</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Reichenbach</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Sterchi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PA</Initials>
<FamilyName>Dieppe</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Egger</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Risk of cardiovascular events and rofecoxib: cumulat
ive meta-analysis</ArticleTitle>
<JournalTitle>Lancet</JournalTitle>
<VolumeID>364</VolumeID>
<IssueID>9450</IssueID>
<FirstPage>2021</FirstPage>
<LastPage>2029</LastPage>
<BibArticleDOI>10.1016/S0140-6736(04)17514-4</BibArticleDOI>
</BibArticle>
<BibUnstructured>Juni P, Nartey L, Reichenbach S, Sterchi R, Dieppe PA, Egger M
(2004) Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. La
ncet 364(9450):2021–2029. doi:10.1016/S0140-6736(04)17514-4</BibUnstructu
red>
</Citation>
<Citation ID="CR73">
<BibArticle>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Kanazawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Soucek</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Evan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Okamoto</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BM</Initials>
<FamilyName>Peterlin</FamilyName>
</BibAuthorName>
<Year>2003</Year>
<ArticleTitle Language="En">c-Myc recruits P-TEFb for transcription, cellular pr
oliferation and apoptosis</ArticleTitle>
<JournalTitle>Oncogene</JournalTitle>
<VolumeID>22</VolumeID>
<IssueID>36</IssueID>
<FirstPage>5707</FirstPage>
<LastPage>5711</LastPage>
<BibArticleDOI>10.1038/sj.onc.1206800</BibArticleDOI>
</BibArticle>
<BibUnstructured>Kanazawa S, Soucek L, Evan G, Okamoto T, Peterlin BM (2003) c-M
yc recruits P-TEFb for transcription, cellular proliferation and apoptosis. Onco
gene 22(36):5707–5711. doi:10.1038/sj.onc.1206800</BibUnstructured>
</Citation>
<Citation ID="CR74">
<BibArticle>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Karha</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EJ</Initials>
<FamilyName>Topol</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">The sad story of Vioxx, and what we should learn fro
m it</ArticleTitle>
<JournalTitle>Cleve Clin J Med</JournalTitle>
<VolumeID>71</VolumeID>
<IssueID>12</IssueID>
<FirstPage>933</FirstPage>
<LastPage>934, 936, 938, 939</LastPage>
</BibArticle>
<BibUnstructured>Karha J, Topol EJ (2004) The sad story of Vioxx, and what we sh
ould learn from it. Cleve Clin J Med 71(12):933–934, 936, 938, 939</BibUn
structured>
</Citation>
<Citation ID="CR75">
<BibArticle>
<BibAuthorName>
<Initials>JH</Initials>
<FamilyName>Kim</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AR</Initials>
<FamilyName>Scialli</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Thalidomide: the tragedy of birth defects and the ef
fective treatment of disease</ArticleTitle>
<JournalTitle>Toxicol Sci</JournalTitle>
<VolumeID>122</VolumeID>
<IssueID>1</IssueID>
<FirstPage>1</FirstPage>
<LastPage>6</LastPage>
<BibArticleDOI>10.1093/toxsci/kfr088</BibArticleDOI>
</BibArticle>
<BibUnstructured>Kim JH, Scialli AR (2011) Thalidomide: the tragedy of birth def
ects and the effective treatment of disease. Toxicol Sci 122(1):1–6. doi:
10.1093/toxsci/kfr088</BibUnstructured>
</Citation>
<Citation ID="CR76">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Kim</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Doi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Wen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Ng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Zhao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Cahan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Kim</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Aryee</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Ji</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LIR</Initials>
<FamilyName>Ehrlich</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Yabuuchi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Takeuchi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KC</Initials>
<FamilyName>Cunniff</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Hongguang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>McKinney-Freeman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Naveiras</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TJ</Initials>
<FamilyName>Yoon</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RA</Initials>
<FamilyName>Irizarry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Jung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Seita</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hanna</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Murakami</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Jaenisch</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Weissleder</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SH</Initials>
<FamilyName>Orkin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>IL</Initials>
<FamilyName>Weissman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AP</Initials>
<FamilyName>Feinberg</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Epigenetic memory in induced pluripotent stem cells<
/ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>467</VolumeID>
<IssueID>7313</IssueID>
<FirstPage>285</FirstPage>
<LastPage>290</LastPage>
<BibArticleDOI>10.1038/nature09342</BibArticleDOI>
</BibArticle>
<BibUnstructured>Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji
H, Ehrlich LIR, Yabuuchi A, Takeuchi A, Cunniff KC, Hongguang H, McKinney-Freem
an S, Naveiras O, Yoon TJ, Irizarry RA, Jung N, Seita J, Hanna J, Murakami P, Ja
enisch R, Weissleder R, Orkin SH, Weissman IL, Feinberg AP, Daley GQ (2010) Epig
enetic memory in induced pluripotent stem cells. Nature 467(7313):285–290
. doi:10.1038/nature09342</BibUnstructured>
</Citation>
<Citation ID="CR77">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Kim</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Zhao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Doi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Ng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Unternaehrer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Cahan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Huo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Loh</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Aryee</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MW</Initials>
<FamilyName>Lensch</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Li</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JJ</Initials>
<FamilyName>Collins</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AP</Initials>
<FamilyName>Feinberg</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Donor cell type can influence the epigenome and diff
erentiation potential of human induced pluripotent stem cells</ArticleTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>29</VolumeID>
<IssueID>12</IssueID>
<FirstPage>1117</FirstPage>
<LastPage>1119</LastPage>
<BibArticleDOI>10.1038/nbt.2052</BibArticleDOI>
</BibArticle>
<BibUnstructured>Kim K, Zhao R, Doi A, Ng K, Unternaehrer J, Cahan P, Huo H, Loh
Y, Aryee MJ, Lensch MW, Li H, Collins JJ, Feinberg AP, Daley GQ (2011) Donor ce
ll type can influence the epigenome and differentiation potential of human induc
ed pluripotent stem cells. Nat Biotechnol 29(12):1117–1119. doi:10.1038/n
bt.2052</BibUnstructured>
</Citation>
<Citation ID="CR78">
<BibArticle>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Kim</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Wong</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Wen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Wang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Wang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Spiering</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NG</Initials>
<FamilyName>Kan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Forcales</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PL</Initials>
<FamilyName>Puri</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TC</Initials>
<FamilyName>Leone</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JE</Initials>
<FamilyName>Marine</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Calkins</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DP</Initials>
<FamilyName>Kelly</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DP</Initials>
<FamilyName>Judge</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HV</Initials>
<FamilyName>Chen</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Studying arrhythmogenic right ventricular dysplasia
with patient-specific iPSCs</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>494</VolumeID>
<IssueID>7435</IssueID>
<FirstPage>105</FirstPage>
<LastPage>110</LastPage>
<BibArticleDOI>10.1038/nature11799</BibArticleDOI>
</BibArticle>
<BibUnstructured>Kim C, Wong J, Wen J, Wang S, Wang C, Spiering S, Kan NG, Forca
les S, Puri PL, Leone TC, Marine JE, Calkins H, Kelly DP, Judge DP, Chen HV (201
3) Studying arrhythmogenic right ventricular dysplasia with patient-specific iPS
Cs. Nature 494(7435):105–110. doi:10.1038/nature11799</BibUnstructured>
</Citation>
<Citation ID="CR79">
<BibUnstructured>Kitaoka S, Kondoh H, Inoue H Induced pluripotent stem cell tech
nology for the study of neurodegenerative diseases. In: Induced stem cells, pp 1
29–142</BibUnstructured>
</Citation>
<Citation ID="CR80">
<BibArticle>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Kolossov</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BK</Initials>
<FamilyName>Fleischmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Q</Initials>
<FamilyName>Liu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Bloch</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Viatchenko-Karpinski</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Manzke</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GJ</Initials>
<FamilyName>Ji</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Bohlen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Addicks</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hescheler</FamilyName>
</BibAuthorName>
<Year>1998</Year>
<ArticleTitle Language="En">Functional characteristics of ES cell-derived cardia
c precursor cells identified by tissue-specific expression of the green fluoresc
ent protein</ArticleTitle>
<JournalTitle>J Cell Biol</JournalTitle>
<VolumeID>143</VolumeID>
<IssueID>7</IssueID>
<FirstPage>2045</FirstPage>
<LastPage>2056</LastPage>
</BibArticle>
<BibUnstructured>Kolossov E, Fleischmann BK, Liu Q, Bloch W, Viatchenko-Karpinsk
i S, Manzke O, Ji GJ, Bohlen H, Addicks K, Hescheler J (1998) Functional charact
eristics of ES cell-derived cardiac precursor cells identified by tissue-specifi
c expression of the green fluorescent protein. J Cell Biol 143(7):2045–20
56</BibUnstructured>
</Citation>
<Citation ID="CR81">
<BibArticle>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Krtolica</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Ilic</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Genbacev</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RK</Initials>
<FamilyName>Miller</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Human embryonic stem cells as a model for embryotoxi
city screening</ArticleTitle>
<JournalTitle>Regen Med</JournalTitle>
<VolumeID>4</VolumeID>
<IssueID>3</IssueID>
<FirstPage>449</FirstPage>
<LastPage>459</LastPage>
<BibArticleDOI>10.2217/rme.09.13</BibArticleDOI>
</BibArticle>
<BibUnstructured>Krtolica A, Ilic D, Genbacev O, Miller RK (2009) Human embryoni
c stem cells as a model for embryotoxicity screening. Regen Med 4(3):449–
459. doi:10.2217/rme.09.13</BibUnstructured>
</Citation>
<Citation ID="CR82">
<BibArticle>
<BibAuthorName>
<Initials>AK</Initials>
<FamilyName>Krug</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Kolde</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Gaspar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Rempel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NV</Initials>
<FamilyName>Balmer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Meganathan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Vojnits</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Baquié</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Waldmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Ensenat-Waser</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Jagtap</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RM</Initials>
<FamilyName>Evans</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Julien</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Peterson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Zagoura</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Kadereit</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Gerhard</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Sotiriadou</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Heke</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Natarajan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Henry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Winkler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Marchan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Stoppini</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bosgra</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Westerhout</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Verwei</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Vilo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Kortenkamp</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hescheler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Hothorn</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Thriel</FamilyName>
<Particle>van</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Krause</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JG</Initials>
<FamilyName>Hengstler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Rahnenführer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Leist</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Sachinidis</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Human embryonic stem cell-derived test systems for d
evelopmental neurotoxicity: a transcriptomics approach</ArticleTitle>
<JournalTitle>Arch Toxicol</JournalTitle>
<VolumeID>87</VolumeID>
<IssueID>1</IssueID>
<FirstPage>123</FirstPage>
<LastPage>143</LastPage>
<BibArticleDOI>10.1007/s00204-012-0967-3</BibArticleDOI>
</BibArticle>
<BibUnstructured>Krug AK, Kolde R, Gaspar JA, Rempel E, Balmer NV, Meganathan K,
Vojnits K, Baquié M, Waldmann T, Ensenat-Waser R, Jagtap S, Evans RM, Ju
lien S, Peterson H, Zagoura D, Kadereit S, Gerhard D, Sotiriadou I, Heke M, Nata
rajan K, Henry M, Winkler J, Marchan R, Stoppini L, Bosgra S, Westerhout J, Verw
ei M, Vilo J, Kortenkamp A, Hescheler J, Hothorn L, Bremer S, van Thriel C, Krau
se K, Hengstler JG, Rahnenführer J, Leist M, Sachinidis A (2013) Human em
bryonic stem cell-derived test systems for developmental neurotoxicity: a transc
riptomics approach. Arch Toxicol 87(1):123–143. doi:10.1007/s00204-012-09
67-3</BibUnstructured>
</Citation>
<Citation ID="CR83">
<BibArticle>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Lazarov</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RA</Initials>
<FamilyName>Marr</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Of mice and men: neurogenesis, cognition and Alzheim
er’s disease</ArticleTitle>
<JournalTitle>Front Aging Neurosci</JournalTitle>
<VolumeID>5</VolumeID>
<FirstPage>43</FirstPage>
<BibArticleDOI>10.3389/fnagi.2013.00043</BibArticleDOI>
</BibArticle>
<BibUnstructured>Lazarov O, Marr RA (2013) Of mice and men: neurogenesis, cognit
ion and Alzheimer’s disease. Front Aging Neurosci 5:43. doi:10.3389/fnagi
.2013.00043</BibUnstructured>
</Citation>
<Citation ID="CR84">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Leist</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Hartung</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Inflammatory findings on species extrapolations: hum
ans are definitely no 70-kg mice</ArticleTitle>
<JournalTitle>ALTEX</JournalTitle>
<VolumeID>30</VolumeID>
<IssueID>2</IssueID>
<FirstPage>227</FirstPage>
<LastPage>230</LastPage>
</BibArticle>
<BibUnstructured>Leist M, Hartung T (2013) Inflammatory findings on species extr
apolations: humans are definitely no 70-kg mice. ALTEX 30(2):227–230</Bib
Unstructured>
</Citation>
<Citation ID="CR85">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Leist</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Ringwald</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Kolde</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Thriel</FamilyName>
<Particle>van</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Krause</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Rahnenführer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Sachinidis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hescheler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JG</Initials>
<FamilyName>Hengstler</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Test systems of developmental toxicity: state-of-the
art and future perspectives</ArticleTitle>
<JournalTitle>Arch Toxicol</JournalTitle>
<VolumeID>87</VolumeID>
<IssueID>12</IssueID>
<FirstPage>2037</FirstPage>
<LastPage>2042</LastPage>
<BibArticleDOI>10.1007/s00204-013-1154-x</BibArticleDOI>
</BibArticle>
<BibUnstructured>Leist M, Ringwald A, Kolde R, Bremer S, van Thriel C, Krause K,
Rahnenführer J, Sachinidis A, Hescheler J, Hengstler JG (2013) Test syst
ems of developmental toxicity: state-of-the art and future perspectives. Arch To
xicol 87(12):2037–2042. doi:10.1007/s00204-013-1154-x</BibUnstructured>
</Citation>
<Citation ID="CR86">
<BibArticle>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Lister</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Pelizzola</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>YS</Initials>
<FamilyName>Kida</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RD</Initials>
<FamilyName>Hawkins</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JR</Initials>
<FamilyName>Nery</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Hon</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Antosiewicz-Bourget</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>O’Malley</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Castanon</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Klugman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Downes</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Yu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Stewart</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Ren</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Thomson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RM</Initials>
<FamilyName>Evans</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JR</Initials>
<FamilyName>Ecker</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Hotspots of aberrant epigenomic reprogramming in hum
an induced pluripotent stem cells</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>471</VolumeID>
<IssueID>7336</IssueID>
<FirstPage>68</FirstPage>
<LastPage>73</LastPage>
<BibArticleDOI>10.1038/nature09798</BibArticleDOI>
</BibArticle>
<BibUnstructured>Lister R, Pelizzola M, Kida YS, Hawkins RD, Nery JR, Hon G, Ant
osiewicz-Bourget J, O’Malley R, Castanon R, Klugman S, Downes M, Yu R, St
ewart R, Ren B, Thomson JA, Evans RM, Ecker JR (2011) Hotspots of aberrant epige
nomic reprogramming in human induced pluripotent stem cells. Nature 471(7336):68
–73. doi:10.1038/nature09798</BibUnstructured>
</Citation>
<Citation ID="CR87">
<BibArticle>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Ma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Xie</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Laurent</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Ding</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Progress in the reprogramming of somatic cells</Arti
cleTitle>
<JournalTitle>Circ Res</JournalTitle>
<VolumeID>112</VolumeID>
<IssueID>3</IssueID>
<FirstPage>562</FirstPage>
<LastPage>574</LastPage>
<BibArticleDOI>10.1161/CIRCRESAHA.111.249235</BibArticleDOI>
</BibArticle>
<BibUnstructured>Ma T, Xie M, Laurent T, Ding S (2013) Progress in the reprogram
ming of somatic cells. Circ Res 112(3):562–574. doi:10.1161/CIRCRESAHA.11
1.249235</BibUnstructured>
</Citation>
<Citation ID="CR88">
<BibArticle>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Malik</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AG</Initials>
<FamilyName>Efthymiou</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Mather</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Chester</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>X</Initials>
<FamilyName>Wang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Nath</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MS</Initials>
<FamilyName>Rao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JP</Initials>
<FamilyName>Steiner</FamilyName>
</BibAuthorName>
<Year>2014</Year>
<ArticleTitle Language="En">Compounds with species and cell type specific toxici
ty identified in a 2000 compound drug screen of neural stem cells and rat mixed
cortical neurons</ArticleTitle>
<JournalTitle>Neurotoxicology</JournalTitle>
<VolumeID>45C</VolumeID>
<FirstPage>192</FirstPage>
<LastPage>200</LastPage>
<BibArticleDOI>10.1016/j.neuro.2014.10.007</BibArticleDOI>
</BibArticle>
<BibUnstructured>Malik N, Efthymiou AG, Mather K, Chester N, Wang X, Nath A, Rao
MS, Steiner JP (2014) Compounds with species and cell type specific toxicity id
entified in a 2000 compound drug screen of neural stem cells and rat mixed corti
cal neurons. Neurotoxicology 45C:192–200. doi:10.1016/j.neuro.2014.10.007
</BibUnstructured>
</Citation>
<Citation ID="CR89">
<BibArticle>
<BibAuthorName>
<Initials>MCN</Initials>
<FamilyName>Marchetto</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AR</Initials>
<FamilyName>Muotri</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Mu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AM</Initials>
<FamilyName>Smith</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GG</Initials>
<FamilyName>Cezar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FH</Initials>
<FamilyName>Gage</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">Non-cell-autonomous effect of human SOD1 G37R astroc
ytes on motor neurons derived from human embryonic stem cells</ArticleTitle>
<JournalTitle>Cell Stem Cell</JournalTitle>
<VolumeID>3</VolumeID>
<IssueID>6</IssueID>
<FirstPage>649</FirstPage>
<LastPage>657</LastPage>
<BibArticleDOI>10.1016/j.stem.2008.10.001</BibArticleDOI>
</BibArticle>
<BibUnstructured>Marchetto MCN, Muotri AR, Mu Y, Smith AM, Cezar GG, Gage FH (20
08) Non-cell-autonomous effect of human SOD1 G37R astrocytes on motor neurons de
rived from human embryonic stem cells. Cell Stem Cell 3(6):649–657. doi:1
0.1016/j.stem.2008.10.001</BibUnstructured>
</Citation>
<Citation ID="CR90">
<BibArticle>
<BibAuthorName>
<Initials>MCN</Initials>
<FamilyName>Marchetto</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Carromeu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Acab</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Yu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GW</Initials>
<FamilyName>Yeo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Mu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Chen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FH</Initials>
<FamilyName>Gage</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AR</Initials>
<FamilyName>Muotri</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">A model for neural development and treatment of Rett
syndrome using human induced pluripotent stem cells</ArticleTitle>
<JournalTitle>Cell</JournalTitle>
<VolumeID>143</VolumeID>
<IssueID>4</IssueID>
<FirstPage>527</FirstPage>
<LastPage>539</LastPage>
<BibArticleDOI>10.1016/j.cell.2010.10.016</BibArticleDOI>
</BibArticle>
<BibUnstructured>Marchetto MCN, Carromeu C, Acab A, Yu D, Yeo GW, Mu Y, Chen G,
Gage FH, Muotri AR (2010) A model for neural development and treatment of Rett s
yndrome using human induced pluripotent stem cells. Cell 143(4):527–539.
doi:10.1016/j.cell.2010.10.016</BibUnstructured>
</Citation>
<Citation ID="CR91">
<BibArticle>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Marx-Stoelting</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Adriaens</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Ahr</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Garthoff</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Gelbke</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Piersma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Pellizzer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>U</Initials>
<FamilyName>Reuter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Rogiers</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Schenk</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Schwengberg</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Seiler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Steemans</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DB</Initials>
<FamilyName>Stedman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Vanparys</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Vericat</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Verwei</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Water</FamilyName>
<Particle>van der</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Weimer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Schwarz</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">A review of the implementation of the embryonic stem
cell test (EST). The report and recommendations of an ECVAM/ReProTect workshop<
/ArticleTitle>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>37</VolumeID>
<IssueID>3</IssueID>
<FirstPage>313</FirstPage>
<LastPage>328</LastPage>
</BibArticle>
<BibUnstructured>Marx-Stoelting P, Adriaens E, Ahr H, Bremer S, Garthoff B, Gelb
ke H, Piersma A, Pellizzer C, Reuter U, Rogiers V, Schenk B, Schwengberg S, Seil
er A, Spielmann H, Steemans M, Stedman DB, Vanparys P, Vericat JA, Verwei M, van
der Water F, Weimer M, Schwarz M (2009) A review of the implementation of the e
mbryonic stem cell test (EST). The report and recommendations of an ECVAM/ReProT
ect workshop. Altern Lab Anim 37(3):313–328</BibUnstructured>
</Citation>
<Citation ID="CR92">
<BibArticle>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>McKernan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FM</Initials>
<FamilyName>Watt</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">What is the point of large-scale collections of huma
<FamilyName>Merkle</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Modeling human disease with pluripotent stem cells:
from genome association to function</ArticleTitle>
<JournalTitle>Cell Stem Cell</JournalTitle>
<VolumeID>12</VolumeID>
<IssueID>6</IssueID>
<FirstPage>656</FirstPage>
<LastPage>668</LastPage>
<BibArticleDOI>10.1016/j.stem.2013.05.016</BibArticleDOI>
</BibArticle>
<BibUnstructured>Merkle FT, Eggan K (2013) Modeling human disease with pluripote
nt stem cells: from genome association to function. Cell Stem Cell 12(6):656
013;668. doi:10.1016/j.stem.2013.05.016</BibUnstructured>
</Citation>
<Citation ID="CR96">
<BibArticle>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Mestas</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CCW</Initials>
<FamilyName>Hughes</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Of mice and not men: differences between mouse and h
uman immunology</ArticleTitle>
<JournalTitle>J Immunol</JournalTitle>
<VolumeID>172</VolumeID>
<IssueID>5</IssueID>
<FirstPage>2731</FirstPage>
<LastPage>2738</LastPage>
</BibArticle>
<BibUnstructured>Mestas J, Hughes CCW (2004) Of mice and not men: differences be
tween mouse and human immunology. J Immunol 172(5):2731–2738</BibUnstruct
ured>
</Citation>
<Citation ID="CR97">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Mitsui</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Tokuzawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Itoh</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Segawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Murakami</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Takahashi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Maruyama</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Maeda</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Yamanaka</FamilyName>
</BibAuthorName>
<Year>2003</Year>
<ArticleTitle Language="En">The homeoprotein Nanog is required for maintenance o
f pluripotency in mouse epiblast and ES cells</ArticleTitle>
<JournalTitle>Cell</JournalTitle>
<VolumeID>113</VolumeID>
<IssueID>5</IssueID>
<FirstPage>631</FirstPage>
<LastPage>642</LastPage>
</BibArticle>
<BibUnstructured>Mitsui K, Tokuzawa Y, Itoh H, Segawa K, Murakami M, Takahashi K
, Maruyama M, Maeda M, Yamanaka S (2003) The homeoprotein Nanog is required for
maintenance of pluripotency in mouse epiblast and ES cells. Cell 113(5):631 
13;642</BibUnstructured>
</Citation>
<Citation ID="CR98">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Miura</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Okada</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Aoi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Okada</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Takahashi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Okita</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Nakagawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Koyanagi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Tanabe</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Ohnuki</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Ogawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Ikeda</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Okano</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Yamanaka</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Variation in the safety of induced pluripotent stem
cell lines</ArticleTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>27</VolumeID>
<IssueID>8</IssueID>
<FirstPage>743</FirstPage>
<LastPage>745</LastPage>
<BibArticleDOI>10.1038/nbt.1554</BibArticleDOI>
</BibArticle>
<BibUnstructured>Miura K, Okada Y, Aoi T, Okada A, Takahashi K, Okita K, Nakagaw
a M, Koyanagi M, Tanabe K, Ohnuki M, Ogawa D, Ikeda E, Okano H, Yamanaka S (2009
) Variation in the safety of induced pluripotent stem cell lines. Nat Biotechnol
27(8):743–745. doi:10.1038/nbt.1554</BibUnstructured>
</Citation>
<Citation ID="CR99">
<BibArticle>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Moretti</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Bellin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Welling</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CB</Initials>
<FamilyName>Jung</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JT</Initials>
<FamilyName>Lam</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Bott-Flugel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Dorn</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Goedel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Hohnke</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Hofmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Seyfarth</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Sinnecker</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Schomig</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Laugwitz</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Patient-specific induced pluripotent stem-cell model
s for long-QT syndrome</ArticleTitle>
<JournalTitle>N Engl J Med</JournalTitle>
<VolumeID>363</VolumeID>
<IssueID>15</IssueID>
<FirstPage>1397</FirstPage>
<LastPage>1409</LastPage>
<BibArticleDOI>10.1056/NEJMoa0908679</BibArticleDOI>
</BibArticle>
<BibUnstructured>Moretti A, Bellin M, Welling A, Jung CB, Lam JT, Bott-Flugel L,
Dorn T, Goedel A, Hohnke C, Hofmann F, Seyfarth M, Sinnecker D, Schomig A, Laug
witz K (2010) Patient-specific induced pluripotent stem-cell models for long-QT
syndrome. N Engl J Med 363(15):1397–1409. doi:10.1056/NEJMoa0908679</BibU
nstructured>
</Citation>
<Citation ID="CR100">
<BibArticle>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Mukherjee</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SE</Initials>
<FamilyName>Nissen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EJ</Initials>
<FamilyName>Topol</FamilyName>
</BibAuthorName>
<Year>2001</Year>
<ArticleTitle Language="En">Risk of cardiovascular events associated with select
ive COX-2 inhibitors</ArticleTitle>
<JournalTitle>JAMA</JournalTitle>
<VolumeID>286</VolumeID>
<IssueID>8</IssueID>
<FirstPage>954</FirstPage>
<LastPage>959</LastPage>
</BibArticle>
<BibUnstructured>Mukherjee D, Nissen SE, Topol EJ (2001) Risk of cardiovascular
events associated with selective COX-2 inhibitors. JAMA 286(8):954–959</B
ibUnstructured>
</Citation>
<Citation ID="CR101">
<BibArticle>
<BibAuthorName>
<Initials>LUW</Initials>
<FamilyName>Müller</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MD</Initials>
<FamilyName>Milsom</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CE</Initials>
<FamilyName>Harris</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Vyas</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KM</Initials>
<FamilyName>Brumme</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Parmar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LA</Initials>
<FamilyName>Moreau</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Schambach</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Park</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>WB</Initials>
<FamilyName>London</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Strait</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Schlaeger</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AL</Initials>
<FamilyName>Devine</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Grassman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>D’Andrea</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DA</Initials>
<FamilyName>Williams</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Overcoming reprogramming resistance of Fanconi anemi
a cells</ArticleTitle>
<JournalTitle>Blood</JournalTitle>
<VolumeID>119</VolumeID>
<IssueID>23</IssueID>
<FirstPage>5449</FirstPage>
<LastPage>5457</LastPage>
<BibArticleDOI>10.1182/blood-2012-02-408674</BibArticleDOI>
</BibArticle>
<BibUnstructured>Müller LUW, Milsom MD, Harris CE, Vyas R, Brumme KM, Par
mar K, Moreau LA, Schambach A, Park I, London WB, Strait K, Schlaeger T, Devine
AL, Grassman E, D’Andrea A, Daley GQ, Williams DA (2012) Overcoming repro
gramming resistance of Fanconi anemia cells. Blood 119(23):5449–5457. doi
:10.1182/blood-2012-02-408674</BibUnstructured>
</Citation>
<Citation ID="CR102">
<BibArticle>
<BibAuthorName>
<Initials>CE</Initials>
<FamilyName>Murry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Keller</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">Differentiation of embryonic stem cells to clinicall
y relevant populations: lessons from embryonic development</ArticleTitle>
<JournalTitle>Cell</JournalTitle>
<VolumeID>132</VolumeID>
<IssueID>4</IssueID>
<FirstPage>661</FirstPage>
<LastPage>680</LastPage>
<BibArticleDOI>10.1016/j.cell.2008.02.008</BibArticleDOI>
</BibArticle>
<BibUnstructured>Murry CE, Keller G (2008) Differentiation of embryonic stem cel
ls to clinically relevant populations: lessons from embryonic development. Cell
132(4):661–680. doi:10.1016/j.cell.2008.02.008</BibUnstructured>
</Citation>
<Citation ID="CR103">
<BibArticle>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Niwa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Miyazaki</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AG</Initials>
<FamilyName>Smith</FamilyName>
</BibAuthorName>
<Year>2000</Year>
<ArticleTitle Language="En">Quantitative expression of Oct-3/4 defines different
iation, dedifferentiation or self-renewal of ES cells</ArticleTitle>
<JournalTitle>Nat Genet</JournalTitle>
<VolumeID>24</VolumeID>
<IssueID>4</IssueID>
<FirstPage>372</FirstPage>
<LastPage>376</LastPage>
<BibArticleDOI>10.1038/74199</BibArticleDOI>
</BibArticle>
<BibUnstructured>Niwa H, Miyazaki J, Smith AG (2000) Quantitative expression of
Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells.
Nat Genet 24(4):372–376. doi:10.1038/74199</BibUnstructured>
</Citation>
<Citation ID="CR104">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Okita</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Ichisaka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Yamanaka</FamilyName>
</BibAuthorName>
<Year>2007</Year>
<ArticleTitle Language="En">Generation of germline-competent induced pluripotent
stem cells</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>448</VolumeID>
<IssueID>7151</IssueID>
<FirstPage>313</FirstPage>
<LastPage>317</LastPage>
<BibArticleDOI>10.1038/nature05934</BibArticleDOI>
</BibArticle>
<BibUnstructured>Okita K, Ichisaka T, Yamanaka S (2007) Generation of germline-c
ompetent induced pluripotent stem cells. Nature 448(7151):313–317. doi:10
.1038/nature05934</BibUnstructured>
</Citation>
<Citation ID="CR105">
<BibArticle>
<BibAuthorName>
<Initials>TT</Initials>
<FamilyName>Onder</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GQ</Initials>
<FamilyName>Daley</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">New lessons learned from disease modeling with induc
ed pluripotent stem cells</ArticleTitle>
<JournalTitle>Curr Opin Genet Dev</JournalTitle>
<VolumeID>22</VolumeID>
<IssueID>5</IssueID>
<FirstPage>500</FirstPage>
<LastPage>508</LastPage>
<BibArticleDOI>10.1016/j.gde.2012.05.005</BibArticleDOI>
</BibArticle>
<BibUnstructured>Onder TT, Daley GQ (2012) New lessons learned from disease mode
ling with induced pluripotent stem cells. Curr Opin Genet Dev 22(5):500–5
08. doi:10.1016/j.gde.2012.05.005</BibUnstructured>
</Citation>
<Citation ID="CR106">
<BibArticle>
<BibAuthorName>
<Initials>AM</Initials>
<FamilyName>Osman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DAM</Initials>
<FamilyName>Dartel</FamilyName>
<Particle>van</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Zwart</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Blokland</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JLA</Initials>
<FamilyName>Pennings</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AH</Initials>
<FamilyName>Piersma</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Proteome profiling of mouse embryonic stem cells to
define markers for cell differentiation and embryotoxicity</ArticleTitle>
<JournalTitle>Reprod Toxicol</JournalTitle>
<VolumeID>30</VolumeID>
<IssueID>2</IssueID>
<FirstPage>322</FirstPage>
<LastPage>332</LastPage>
<BibArticleDOI>10.1016/j.reprotox.2010.05.084</BibArticleDOI>
</BibArticle>
<BibUnstructured>Osman AM, van Dartel DAM, Zwart E, Blokland M, Pennings JLA, Pi
ersma AH (2010) Proteome profiling of mouse embryonic stem cells to define marke
rs for cell differentiation and embryotoxicity. Reprod Toxicol 30(2):322–
332. doi:10.1016/j.reprotox.2010.05.084</BibUnstructured>
</Citation>
<Citation ID="CR107">
<BibArticle>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Perel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Roberts</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Sena</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Wheble</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Briscoe</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Sandercock</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Macleod</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LE</Initials>
<FamilyName>Mignini</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Jayaram</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KS</Initials>
<FamilyName>Khan</FamilyName>
</BibAuthorName>
<Year>2007</Year>
<ArticleTitle Language="En">Comparison of treatment effects between animal exper
iments and clinical trials: systematic review</ArticleTitle>
<JournalTitle>BMJ</JournalTitle>
<VolumeID>334</VolumeID>
<IssueID>7586</IssueID>
<FirstPage>197</FirstPage>
<BibArticleDOI>10.1136/bmj.39048.407928.BE</BibArticleDOI>
</BibArticle>
<BibUnstructured>Perel P, Roberts I, Sena E, Wheble P, Briscoe C, Sandercock P,
Macleod M, Mignini LE, Jayaram P, Khan KS (2007) Comparison of treatment effects
between animal experiments and clinical trials: systematic review. BMJ 334(7586
):197. doi:10.1136/bmj.39048.407928.BE</BibUnstructured>
</Citation>
<Citation ID="CR108">
<BibArticle>
<BibAuthorName>
<Initials>AH</Initials>
<FamilyName>Piersma</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Validation of alternative methods for developmental
toxicity testing</ArticleTitle>
<JournalTitle>Toxicol Lett</JournalTitle>
<VolumeID>149</VolumeID>
<IssueID>1–3</IssueID>
<FirstPage>147</FirstPage>
<LastPage>153</LastPage>
<BibArticleDOI>10.1016/j.toxlet.2003.12.029</BibArticleDOI>
</BibArticle>
<BibUnstructured>Piersma AH (2004) Validation of alternative methods for develop
mental toxicity testing. Toxicol Lett 149(1–3):147–153. doi:10.101
6/j.toxlet.2003.12.029</BibUnstructured>
</Citation>
<Citation ID="CR109">
<BibArticle>
<BibAuthorName>
<Initials>JM</Initials>
<FamilyName>Polo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Liu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>ME</Initials>
<FamilyName>Figueroa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Kulalert</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Eminli</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KY</Initials>
<FamilyName>Tan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Apostolou</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Stadtfeld</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Li</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Shioda</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Natesan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AJ</Initials>
<FamilyName>Wagers</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Melnick</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Evans</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Hochedlinger</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Cell type of origin influences the molecular and fun
ctional properties of mouse induced pluripotent stem cells</ArticleTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>28</VolumeID>
<IssueID>8</IssueID>
<FirstPage>848</FirstPage>
<LastPage>855</LastPage>
<BibArticleDOI>10.1038/nbt.1667</BibArticleDOI>
</BibArticle>
<BibUnstructured>Polo JM, Liu S, Figueroa ME, Kulalert W, Eminli S, Tan KY, Apos
tolou E, Stadtfeld M, Li Y, Shioda T, Natesan S, Wagers AJ, Melnick A, Evans T,
Hochedlinger K (2010) Cell type of origin influences the molecular and functiona
l properties of mouse induced pluripotent stem cells. Nat Biotechnol 28(8):848&#
x2013;855. doi:10.1038/nbt.1667</BibUnstructured>
</Citation>
<Citation ID="CR110">
<BibArticle>
<BibAuthorName>
<Initials>NM</Initials>
<FamilyName>Radio</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>WR</Initials>
<FamilyName>Mundy</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">Developmental neurotoxicity testing in vitro: models
for assessing chemical effects on neurite outgrowth</ArticleTitle>
<JournalTitle>Neurotoxicology</JournalTitle>
<VolumeID>29</VolumeID>
<IssueID>3</IssueID>
<FirstPage>361</FirstPage>
<LastPage>376</LastPage>
<BibArticleDOI>10.1016/j.neuro.2008.02.011</BibArticleDOI>
</BibArticle>
<BibUnstructured>Radio NM, Mundy WR (2008) Developmental neurotoxicity testing i
n vitro: models for assessing chemical effects on neurite outgrowth. Neurotoxico
logy 29(3):361–376. doi:10.1016/j.neuro.2008.02.011</BibUnstructured>
</Citation>
<Citation ID="CR111">
<BibArticle>
<BibAuthorName>
<Initials>ST</Initials>
<FamilyName>Rashid</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Corbineau</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Hannan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SJ</Initials>
<FamilyName>Marciniak</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Miranda</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Alexander</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Huang-Doran</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Griffin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Ahrlund-Richter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Skepper</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Semple</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Weber</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DA</Initials>
<FamilyName>Lomas</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Vallier</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Modeling inherited metabolic disorders of the liver
using human induced pluripotent stem cells</ArticleTitle>
<JournalTitle>J Clin Invest</JournalTitle>
<VolumeID>120</VolumeID>
<IssueID>9</IssueID>
<FirstPage>3127</FirstPage>
<LastPage>3136</LastPage>
<BibArticleDOI>10.1172/JCI43122</BibArticleDOI>
</BibArticle>
<BibUnstructured>Rashid ST, Corbineau S, Hannan N, Marciniak SJ, Miranda E, Alex
ander G, Huang-Doran I, Griffin J, Ahrlund-Richter L, Skepper J, Semple R, Weber
A, Lomas DA, Vallier L (2010) Modeling inherited metabolic disorders of the liv
er using human induced pluripotent stem cells. J Clin Invest 120(9):3127–
3136. doi:10.1172/JCI43122</BibUnstructured>
</Citation>
<Citation ID="CR112">
<BibArticle>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Raya</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>I</Initials>
<FamilyName>Rodriguez-Piza</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Guenechea</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Vassena</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Navarro</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Barrero</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Consiglio</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Castella</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Rio</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Sleep</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Gonzalez</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Tiscornia</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Garreta</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Aasen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Veiga</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>IM</Initials>
<FamilyName>Verma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Surralles</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Bueren</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JCI</Initials>
<FamilyName>Belmonte</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Disease-corrected haematopoietic progenitors from Fa
nconi anaemia induced pluripotent stem cells</ArticleTitle>
<JournalTitle>Nature</JournalTitle>
<VolumeID>460</VolumeID>
<IssueID>7251</IssueID>
<FirstPage>53</FirstPage>
<LastPage>59</LastPage>
<BibArticleDOI>10.1038/nature08129</BibArticleDOI>
</BibArticle>
<BibUnstructured>Raya A, Rodriguez-Piza I, Guenechea G, Vassena R, Navarro S, Ba
rrero MJ, Consiglio A, Castella M, Rio P, Sleep E, Gonzalez F, Tiscornia G, Garr
eta E, Aasen T, Veiga A, Verma IM, Surralles J, Bueren J, Belmonte JCI (2009) Di
sease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripot
ent stem cells. Nature 460(7251):53–59. doi:10.1038/nature08129</BibUnstr
uctured>
</Citation>
<Citation ID="CR113">
<BibArticle>
<BibAuthorName>
<Initials>BE</Initials>
<FamilyName>Reubinoff</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Itsykson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Turetsky</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MF</Initials>
<FamilyName>Pera</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Reinhartz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Itzik</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Ben-Hur</FamilyName>
</BibAuthorName>
<Year>2001</Year>
<ArticleTitle Language="En">Neural progenitors from human embryonic stem cells</
ArticleTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>19</VolumeID>
<IssueID>12</IssueID>
<FirstPage>1134</FirstPage>
<LastPage>1140</LastPage>
<BibArticleDOI>10.1038/nbt1201-1134</BibArticleDOI>
</BibArticle>
<BibUnstructured>Reubinoff BE, Itsykson P, Turetsky T, Pera MF, Reinhartz E, Itz
ik A, Ben-Hur T (2001) Neural progenitors from human embryonic stem cells. Nat B
iotechnol 19(12):1134–1140. doi:10.1038/nbt1201-1134</BibUnstructured>
</Citation>
<Citation ID="CR114">
<BibArticle>
<BibAuthorName>
<Initials>RD</Initials>
<FamilyName>Robbins</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Prasain</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BF</Initials>
<FamilyName>Maier</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MC</Initials>
<FamilyName>Yoder</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RG</Initials>
<FamilyName>Mirmira</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Inducible pluripotent stem cells: not quite ready fo
r prime time?</ArticleTitle>
<JournalTitle>Curr Opin Organ Transplant</JournalTitle>
<VolumeID>15</VolumeID>
<IssueID>1</IssueID>
<FirstPage>61</FirstPage>
<LastPage>67</LastPage>
<BibArticleDOI>10.1097/MOT.0b013e3283337196</BibArticleDOI>
</BibArticle>
<BibUnstructured>Robbins RD, Prasain N, Maier BF, Yoder MC, Mirmira RG (2010) In
ducible pluripotent stem cells: not quite ready for prime time? Curr Opin Organ
Transplant 15(1):61–67. doi:10.1097/MOT.0b013e3283337196</BibUnstructured
>
</Citation>
<Citation ID="CR115">
<BibArticle>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Rocha</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Labopin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Sanz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Arcese</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Schwerdtfeger</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Bosi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Jacobsen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Ruutu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Lima</FamilyName>
<Particle>de</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Finke</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Frassoni</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Gluckman</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Transplants of umbilical-cord blood or bone marrow f
rom unrelated donors in adults with acute leukemia</ArticleTitle>
<JournalTitle>N Engl J Med</JournalTitle>
<VolumeID>351</VolumeID>
<IssueID>22</IssueID>
<FirstPage>2276</FirstPage>
<LastPage>2285</LastPage>
<BibArticleDOI>10.1056/NEJMoa041469</BibArticleDOI>
</BibArticle>
<BibUnstructured>Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A,
Jacobsen N, Ruutu T, de Lima M, Finke J, Frassoni F, Gluckman E (2004) Transplan
ts of umbilical-cord blood or bone marrow from unrelated donors in adults with a
cute leukemia. N Engl J Med 351(22):2276–2285. doi:10.1056/NEJMoa041469</
BibUnstructured>
</Citation>
<Citation ID="CR116">
<BibArticle>
<BibAuthorName>
<Initials>MD</Initials>
<FamilyName>Roth-Cline</FamilyName>
</BibAuthorName>
<Year>2006</Year>
<ArticleTitle Language="En">Clinical trials in the wake of Vioxx: requiring stat
istically extreme evidence of benefit to ensure the safety of new drugs</Article
Title>
<JournalTitle>Circulation</JournalTitle>
<VolumeID>113</VolumeID>
<IssueID>18</IssueID>
<FirstPage>2253</FirstPage>
<LastPage>2259</LastPage>
<BibArticleDOI>10.1161/CIRCULATIONAHA.105.604512</BibArticleDOI>
</BibArticle>
<BibUnstructured>Roth-Cline MD (2006) Clinical trials in the wake of Vioxx: requ
iring statistically extreme evidence of benefit to ensure the safety of new drug
s. Circulation 113(18):2253–2259. doi:10.1161/CIRCULATIONAHA.105.604512</
BibUnstructured>
</Citation>
<Citation ID="CR117">
<BibArticle>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Rovida</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Vivier</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Garthoff</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hescheler</FamilyName>
</BibAuthorName>
<Year>2014</Year>
<ArticleTitle Language="En">ESNATS conference – the use of human embryoni
c stem cells for novel toxicity testing approaches</ArticleTitle>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>42</VolumeID>
<IssueID>2</IssueID>
<FirstPage>97</FirstPage>
<LastPage>113</LastPage>
</BibArticle>
<BibUnstructured>Rovida C, Vivier M, Garthoff B, Hescheler J (2014) ESNATS confe
rence – the use of human embryonic stem cells for novel toxicity testing
approaches. Altern Lab Anim 42(2):97–113</BibUnstructured>
</Citation>
<Citation ID="CR118">
<BibUnstructured>Roy ASA (2012) Stifling new cures: the true cost of lengthy cli
nical drug trials. Project FDA report(05)</BibUnstructured>
</Citation>
<Citation ID="CR119">
<BibArticle>
<BibAuthorName>
<Initials>TW</Initials>
<FamilyName>Sadler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>WE</Initials>
<FamilyName>Horton</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CW</Initials>
<FamilyName>Warner</FamilyName>
</BibAuthorName>
<Year>1982</Year>
<ArticleTitle Language="En">Whole embryo culture: a screening technique for tera
togens?</ArticleTitle>
<JournalTitle>Teratog Carcinog Mutagen</JournalTitle>
<VolumeID>2</VolumeID>
<IssueID>3–4</IssueID>
<FirstPage>243</FirstPage>
<LastPage>253</LastPage>
</BibArticle>
<BibUnstructured>Sadler TW, Horton WE, Warner CW (1982) Whole embryo culture: a
screening technique for teratogens? Teratog Carcinog Mutagen 2(3–4):243&#
x2013;253</BibUnstructured>
</Citation>
<Citation ID="CR120">
<BibArticle>
<BibAuthorName>
<Initials>MM</Initials>
<FamilyName>Schmidt</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Guan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AM</Initials>
<FamilyName>Wobus</FamilyName>
</BibAuthorName>
<Year>2001</Year>
<ArticleTitle Language="En">Lithium influences differentiation and tissue-specif
ic gene expression of mouse embryonic stem (ES) cells in vitro</ArticleTitle>
<JournalTitle>Int J Dev Biol</JournalTitle>
<VolumeID>45</VolumeID>
<IssueID>2</IssueID>
<FirstPage>421</FirstPage>
<LastPage>429</LastPage>
</BibArticle>
<BibUnstructured>Schmidt MM, Guan K, Wobus AM (2001) Lithium influences differen
tiation and tissue-specific gene expression of mouse embryonic stem (ES) cells i
n vitro. Int J Dev Biol 45(2):421–429</BibUnstructured>
</Citation>
<Citation ID="CR121">
<BibArticle>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Schoeters</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">The REACH perspective: toward a new concept of toxic
ity testing</ArticleTitle>
<JournalTitle>J Toxicol Environ Health B Crit Rev</JournalTitle>
<VolumeID>13</VolumeID>
<IssueID>2–4</IssueID>
<FirstPage>232</FirstPage>
<LastPage>241</LastPage>
<BibArticleDOI>10.1080/10937404.2010.483938</BibArticleDOI>
</BibArticle>
<BibUnstructured>Schoeters G (2010) The REACH perspective: toward a new concept
of toxicity testing. J Toxicol Environ Health B Crit Rev 13(2–4):232 
13;241. doi:10.1080/10937404.2010.483938</BibUnstructured>
</Citation>
<Citation ID="CR122">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Schuldiner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Yanuka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Itskovitz-Eldor</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DA</Initials>
<FamilyName>Melton</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Benvenisty</FamilyName>
</BibAuthorName>
<Year>2000</Year>
<ArticleTitle Language="En">Effects of eight growth factors on the differentiati
on of cells derived from human embryonic stem cells</ArticleTitle>
<JournalTitle>Proc Natl Acad Sci U S A</JournalTitle>
<VolumeID>97</VolumeID>
<IssueID>21</IssueID>
<FirstPage>11307</FirstPage>
<LastPage>11312</LastPage>
<BibArticleDOI>10.1073/pnas.97.21.11307</BibArticleDOI>
</BibArticle>
<BibUnstructured>Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenist
y N (2000) Effects of eight growth factors on the differentiation of cells deriv
ed from human embryonic stem cells. Proc Natl Acad Sci U S A 97(21):11307–
;11312. doi:10.1073/pnas.97.21.11307</BibUnstructured>
</Citation>
<Citation ID="CR123">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Schuldiner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Eiges</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Eden</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>O</Initials>
<FamilyName>Yanuka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Itskovitz-Eldor</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RS</Initials>
<FamilyName>Goldstein</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Benvenisty</FamilyName>
</BibAuthorName>
<Year>2001</Year>
<ArticleTitle Language="En">Induced neuronal differentiation of human embryonic
stem cells</ArticleTitle>
<JournalTitle>Brain Res</JournalTitle>
<VolumeID>913</VolumeID>
<IssueID>2</IssueID>
<FirstPage>201</FirstPage>
<LastPage>205</LastPage>
</BibArticle>
<BibUnstructured>Schuldiner M, Eiges R, Eden A, Yanuka O, Itskovitz-Eldor J, Gol
dstein RS, Benvenisty N (2001) Induced neuronal differentiation of human embryon
ic stem cells. Brain Res 913(2):201–205</BibUnstructured>
</Citation>
<Citation ID="CR124">
<BibArticle>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Schumacher</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DA</Initials>
<FamilyName>Blake</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JM</Initials>
<FamilyName>Gurian</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JR</Initials>
<FamilyName>Gillette</FamilyName>
</BibAuthorName>
<Year>1968</Year>
<ArticleTitle Language="En">A comparison of the teratogenic activity of thalidom
ide in rabbits and rats</ArticleTitle>
<JournalTitle>J Pharmacol Exp Ther</JournalTitle>
<VolumeID>160</VolumeID>
<IssueID>1</IssueID>
<FirstPage>189</FirstPage>
<LastPage>200</LastPage>
</BibArticle>
<BibUnstructured>Schumacher H, Blake DA, Gurian JM, Gillette JR (1968) A compari
son of the teratogenic activity of thalidomide in rabbits and rats. J Pharmacol
Exp Ther 160(1):189–200</BibUnstructured>
</Citation>
<Citation ID="CR125">
<BibArticle>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Sebastiano</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>ML</Initials>
<FamilyName>Maeder</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JF</Initials>
<FamilyName>Angstman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Haddad</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Khayter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DT</Initials>
<FamilyName>Yeo</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Goodwin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JS</Initials>
<FamilyName>Hawkins</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CL</Initials>
<FamilyName>Ramirez</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LFZ</Initials>
<FamilyName>Batista</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SE</Initials>
<FamilyName>Artandi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Wernig</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JK</Initials>
<FamilyName>Joung</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">In situ genetic correction of the sickle cell anemia
mutation in human induced pluripotent stem cells using engineered zinc finger n
ucleases</ArticleTitle>
<JournalTitle>Stem Cells</JournalTitle>
<VolumeID>29</VolumeID>
<IssueID>11</IssueID>
<FirstPage>1717</FirstPage>
<LastPage>1726</LastPage>
<BibArticleDOI>10.1002/stem.718</BibArticleDOI>
</BibArticle>
<BibUnstructured>Sebastiano V, Maeder ML, Angstman JF, Haddad B, Khayter C, Yeo
DT, Goodwin MJ, Hawkins JS, Ramirez CL, Batista LFZ, Artandi SE, Wernig M, Joung
JK (2011) In situ genetic correction of the sickle cell anemia mutation in huma
n induced pluripotent stem cells using engineered zinc finger nucleases. Stem Ce
lls 29(11):1717–1726. doi:10.1002/stem.718</BibUnstructured>
</Citation>
<Citation ID="CR126">
<BibArticle>
<BibAuthorName>
<Initials>AEM</Initials>
<FamilyName>Seiler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<Year>2011</Year>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Hayess</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Schlechter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Visan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Genschow</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Slawik</FamilyName>
</BibAuthorName>
<Year>2006</Year>
<ArticleTitle Language="En">Current status of the embryonic stem cell test: the
use of recent advances in the field of stem cell technology and gene expression
analysis</ArticleTitle>
<JournalTitle>ALTEX</JournalTitle>
<VolumeID>23</VolumeID>
<FirstPage>393</FirstPage>
<LastPage>399</LastPage>
</BibArticle>
<BibUnstructured>Seiler A, Buesen B, Hayess K, Schlechter K, Visan A, Genschow E
, Slawik B (2006) Current status of the embryonic stem cell test: the use of rec
ent advances in the field of stem cell technology and gene expression analysis.
ALTEX 23:393–399</BibUnstructured>
</Citation>
<Citation ID="CR129">
<BibArticle>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Seok</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HS</Initials>
<FamilyName>Warren</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AG</Initials>
<FamilyName>Cuenca</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MN</Initials>
<FamilyName>Mindrinos</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HV</Initials>
<FamilyName>Baker</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Xu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DR</Initials>
<FamilyName>Richards</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GP</Initials>
<FamilyName>McDonald-Smith</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Gao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Hennessy</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CC</Initials>
<FamilyName>Finnerty</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CM</Initials>
<FamilyName>Lopez</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Honari</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EE</Initials>
<FamilyName>Moore</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JP</Initials>
<FamilyName>Minei</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Cuschieri</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PE</Initials>
<FamilyName>Bankey</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JL</Initials>
<FamilyName>Johnson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Sperry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AB</Initials>
<FamilyName>Nathens</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TR</Initials>
<FamilyName>Billiar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MA</Initials>
<FamilyName>West</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MG</Initials>
<FamilyName>Jeschke</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MB</Initials>
<FamilyName>Klein</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RL</Initials>
<FamilyName>Gamelli</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>NS</Initials>
<FamilyName>Gibran</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BH</Initials>
<FamilyName>Brownstein</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Miller-Graziano</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SE</Initials>
<FamilyName>Calvano</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PH</Initials>
<FamilyName>Mason</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JP</Initials>
<FamilyName>Cobb</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LG</Initials>
<FamilyName>Rahme</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SF</Initials>
<FamilyName>Lowry</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RV</Initials>
<FamilyName>Maier</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LL</Initials>
<FamilyName>Moldawer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DN</Initials>
<FamilyName>Herndon</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RW</Initials>
<FamilyName>Davis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>W</Initials>
<FamilyName>Xiao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RG</Initials>
<FamilyName>Tompkins</FamilyName>
</BibAuthorName>
<Year>2013</Year>
<ArticleTitle Language="En">Genomic responses in mouse models poorly mimic human
inflammatory diseases</ArticleTitle>
<JournalTitle>Proc Natl Acad Sci U S A</JournalTitle>
<VolumeID>110</VolumeID>
<IssueID>9</IssueID>
<FirstPage>3507</FirstPage>
<LastPage>3512</LastPage>
<BibArticleDOI>10.1073/pnas.1222878110</BibArticleDOI>
</BibArticle>
<BibUnstructured>Seok J, Warren HS, Cuenca AG, Mindrinos MN, Baker HV, Xu W, Ric
hards DR, McDonald-Smith GP, Gao H, Hennessy L, Finnerty CC, Lopez CM, Honari S,
Moore EE, Minei JP, Cuschieri J, Bankey PE, Johnson JL, Sperry J, Nathens AB, B
illiar TR, West MA, Jeschke MG, Klein MB, Gamelli RL, Gibran NS, Brownstein BH,
Miller-Graziano C, Calvano SE, Mason PH, Cobb JP, Rahme LG, Lowry SF, Maier RV,
Moldawer LL, Herndon DN, Davis RW, Xiao W, Tompkins RG (2013) Genomic responses
in mouse models poorly mimic human inflammatory diseases. Proc Natl Acad Sci U S
A 110(9):3507–3512. doi:10.1073/pnas.1222878110</BibUnstructured>
</Citation>
<Citation ID="CR130">
<BibArticle>
<BibAuthorName>
<Initials>SD</Initials>
<FamilyName>Sheridan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KM</Initials>
<FamilyName>Theriault</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SA</Initials>
<FamilyName>Reis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Zhou</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JM</Initials>
<FamilyName>Madison</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Daheron</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JF</Initials>
<FamilyName>Loring</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SJ</Initials>
<FamilyName>Haggarty</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Epigenetic characterization of the FMR1 gene and abe
rrant neurodevelopment in human induced pluripotent stem cell models of fragile
X syndrome</ArticleTitle>
<JournalTitle>PLoS One</JournalTitle>
<VolumeID>6</VolumeID>
<IssueID>10</IssueID>
<FirstPage>e26203</FirstPage>
<BibArticleDOI>10.1371/journal.pone.0026203</BibArticleDOI>
</BibArticle>
<BibUnstructured>Sheridan SD, Theriault KM, Reis SA, Zhou F, Madison JM, Daheron
L, Loring JF, Haggarty SJ (2011) Epigenetic characterization of the FMR1 gene a
nd aberrant neurodevelopment in human induced pluripotent stem cell models of fr
agile X syndrome. PLoS One 6(10):e26203. doi:10.1371/journal.pone.0026203</BibUn
structured>
</Citation>
<Citation ID="CR131">
<BibArticle>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Soldner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Jaenisch</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Medicine. iPSC disease modeling</ArticleTitle>
<JournalTitle>Science</JournalTitle>
<VolumeID>338</VolumeID>
<IssueID>6111</IssueID>
<FirstPage>1155</FirstPage>
<LastPage>1156</LastPage>
<BibArticleDOI>10.1126/science.1227682</BibArticleDOI>
</BibArticle>
<BibUnstructured>Soldner F, Jaenisch R (2012) Medicine. iPSC disease modeling. S
cience 338(6111):1155–1156. doi:10.1126/science.1227682</BibUnstructured>
</Citation>
<Citation ID="CR132">
<BibArticle>
<BibAuthorName>
<Initials>F</Initials>
<FamilyName>Soldner</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Laganiere</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AW</Initials>
<FamilyName>Cheng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Hockemeyer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Q</Initials>
<FamilyName>Gao</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Alagappan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Khurana</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LI</Initials>
<FamilyName>Golbe</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RH</Initials>
<FamilyName>Myers</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Lindquist</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Guschin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LK</Initials>
<FamilyName>Fong</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BJ</Initials>
<FamilyName>Vu</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>X</Initials>
<FamilyName>Meng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>FD</Initials>
<FamilyName>Urnov</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>EJ</Initials>
<FamilyName>Rebar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PD</Initials>
<FamilyName>Gregory</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HS</Initials>
<FamilyName>Zhang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Jaenisch</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Generation of isogenic pluripotent stem cells differ
ing exclusively at two early onset Parkinson point mutations</ArticleTitle>
<JournalTitle>Cell</JournalTitle>
<VolumeID>146</VolumeID>
<IssueID>2</IssueID>
<FirstPage>318</FirstPage>
<LastPage>331</LastPage>
<BibArticleDOI>10.1016/j.cell.2011.06.019</BibArticleDOI>
</BibArticle>
<BibUnstructured>Soldner F, Laganiere J, Cheng AW, Hockemeyer D, Gao Q, Alagappa
n R, Khurana V, Golbe LI, Myers RH, Lindquist S, Zhang L, Guschin D, Fong LK, Vu
BJ, Meng X, Urnov FD, Rebar EJ, Gregory PD, Zhang HS, Jaenisch R (2011) Generat
ion of isogenic pluripotent stem cells differing exclusively at two early onset
Parkinson point mutations. Cell 146(2):318–331. doi:10.1016/j.cell.2011.0
6.019</BibUnstructured>
</Citation>
<Citation ID="CR133">
<BibArticle>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">The way forward in reproductive/developmental toxici
ty testing</ArticleTitle>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>37</VolumeID>
<IssueID>6</IssueID>
<FirstPage>641</FirstPage>
<LastPage>656</LastPage>
</BibArticle>
<BibUnstructured>Spielmann H (2009) The way forward in reproductive/developmenta
l toxicity testing. Altern Lab Anim 37(6):641–656</BibUnstructured>
</Citation>
<Citation ID="CR134">
<BibArticle>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Spielmann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Liebsch</FamilyName>
</BibAuthorName>
<Year>2001</Year>
<ArticleTitle Language="En">Lessons learned from validation of in vitro toxicity
test: from failure to acceptance into regulatory practice</ArticleTitle>
<JournalTitle>Toxicol In Vitro</JournalTitle>
<VolumeID>15</VolumeID>
<IssueID>4–5</IssueID>
<FirstPage>585</FirstPage>
<LastPage>590</LastPage>
</BibArticle>
<FamilyName>Ahr</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>E</Initials>
<FamilyName>Faustman</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>U</Initials>
<FamilyName>Haas</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GJ</Initials>
<FamilyName>Moffat</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Nau</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Vanparys</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Piersma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JR</Initials>
<FamilyName>Sintes</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Stuart</FamilyName>
</BibAuthorName>
<Year>2006</Year>
<ArticleTitle Language="En">The practical application of three validated in vitr
o embryotoxicity tests. The report and recommendations of an ECVAM/ZEBET worksho
p (ECVAM workshop 57)</ArticleTitle>
<JournalTitle>Altern Lab Anim</JournalTitle>
<VolumeID>34</VolumeID>
<IssueID>5</IssueID>
<FirstPage>527</FirstPage>
<LastPage>538</LastPage>
</BibArticle>
<BibUnstructured>Spielmann H, Seiler A, Bremer S, Hareng L, Hartung T, Ahr H, Fa
ustman E, Haas U, Moffat GJ, Nau H, Vanparys P, Piersma A, Sintes JR, Stuart J (
2006) The practical application of three validated in vitro embryotoxicity tests
. The report and recommendations of an ECVAM/ZEBET workshop (ECVAM workshop 57).
Altern Lab Anim 34(5):527–538</BibUnstructured>
</Citation>
<Citation ID="CR137">
<BibArticle>
<BibAuthorName>
<Initials>TC</Initials>
<FamilyName>Stummann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Hareng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<Year>2007</Year>
<ArticleTitle Language="En">Embryotoxicity hazard assessment of methylmercury an
d chromium using embryonic stem cells</ArticleTitle>
<JournalTitle>Toxicology</JournalTitle>
<VolumeID>242</VolumeID>
<IssueID>1–3</IssueID>
<FirstPage>130</FirstPage>
<LastPage>143</LastPage>
<BibArticleDOI>10.1016/j.tox.2007.09.022</BibArticleDOI>
</BibArticle>
<BibUnstructured>Stummann TC, Hareng L, Bremer S (2007) Embryotoxicity hazard as
sessment of methylmercury and chromium using embryonic stem cells. Toxicology 24
2(1–3):130–143. doi:10.1016/j.tox.2007.09.022</BibUnstructured>
</Citation>
<Citation ID="CR138">
<BibArticle>
<BibAuthorName>
<Initials>TC</Initials>
<FamilyName>Stummann</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Hareng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Bremer</FamilyName>
</BibAuthorName>
<Year>2009</Year>
<ArticleTitle Language="En">Hazard assessment of methylmercury toxicity to neuro
nal induction in embryogenesis using human embryonic stem cells</ArticleTitle>
<JournalTitle>Toxicology</JournalTitle>
<VolumeID>257</VolumeID>
<IssueID>3</IssueID>
<FirstPage>117</FirstPage>
<LastPage>126</LastPage>
<BibArticleDOI>10.1016/j.tox.2008.12.018</BibArticleDOI>
</BibArticle>
<BibUnstructured>Stummann TC, Hareng L, Bremer S (2009) Hazard assessment of met
hylmercury toxicity to neuronal induction in embryogenesis using human embryonic
stem cells. Toxicology 257(3):117–126. doi:10.1016/j.tox.2008.12.018</Bi
bUnstructured>
</Citation>
<Citation ID="CR139">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Takahashi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Tanabe</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Ohnuki</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Narita</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Ichisaka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Tomoda</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Yamanaka</FamilyName>
</BibAuthorName>
<Year>2007</Year>
<ArticleTitle Language="En">Induction of pluripotent stem cells from adult human
fibroblasts by defined factors</ArticleTitle>
<JournalTitle>Cell</JournalTitle>
<VolumeID>131</VolumeID>
<IssueID>5</IssueID>
<FirstPage>861</FirstPage>
<LastPage>872</LastPage>
<BibArticleDOI>10.1016/j.cell.2007.11.019</BibArticleDOI>
</BibArticle>
<BibUnstructured>Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K
, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibrobl
asts by defined factors. Cell 131(5):861–872. doi:10.1016/j.cell.2007.11.
019</BibUnstructured>
</Citation>
<Citation ID="CR140">
<BibArticle>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Teoh</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Cheong</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Induced pluripotent stem cells in research and thera
py</ArticleTitle>
<JournalTitle>Malays J Pathol</JournalTitle>
<VolumeID>34</VolumeID>
<IssueID>1</IssueID>
<FirstPage>1</FirstPage>
<LastPage>13</LastPage>
</BibArticle>
<BibUnstructured>Teoh H, Cheong S (2012) Induced pluripotent stem cells in resea
rch and therapy. Malays J Pathol 34(1):1–13</BibUnstructured>
</Citation>
<Citation ID="CR141">
<BibArticle>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Thomson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Itskovitz-Eldor</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SS</Initials>
<FamilyName>Shapiro</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MA</Initials>
<FamilyName>Waknitz</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JJ</Initials>
<FamilyName>Swiergiel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>VS</Initials>
<FamilyName>Marshall</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JM</Initials>
<FamilyName>Jones</FamilyName>
</BibAuthorName>
<Year>1998</Year>
<ArticleTitle Language="En">Embryonic stem cell lines derived from human blastoc
ysts</ArticleTitle>
<JournalTitle>Science</JournalTitle>
<VolumeID>282</VolumeID>
<IssueID>5391</IssueID>
<FirstPage>1145</FirstPage>
<LastPage>1147</LastPage>
</BibArticle>
<BibUnstructured>Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergie
l JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human
blastocysts. Science 282(5391):1145–1147</BibUnstructured>
</Citation>
<Citation ID="CR142">
<BibArticle>
<BibAuthorName>
<Initials>LM</Initials>
<FamilyName>Title</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Giddens</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MM</Initials>
<FamilyName>McInerney</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>McQueen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BA</Initials>
<FamilyName>Nassar</FamilyName>
</BibAuthorName>
<Year>2003</Year>
<FamilyName>Worp</FamilyName>
<Particle>van der</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>DW</Initials>
<FamilyName>Howells</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>ES</Initials>
<FamilyName>Sena</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MJ</Initials>
<FamilyName>Porritt</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Rewell</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>O’Collins</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MR</Initials>
<FamilyName>Macleod</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">Can animal models of disease reliably inform human s
tudies?</ArticleTitle>
<JournalTitle>PLoS Med</JournalTitle>
<VolumeID>7</VolumeID>
<IssueID>3</IssueID>
<FirstPage>e1000245</FirstPage>
<BibArticleDOI>10.1371/journal.pmed.1000245</BibArticleDOI>
</BibArticle>
<BibUnstructured>van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O&#
x2019;Collins V, Macleod MR (2010) Can animal models of disease reliably inform
human studies? PLoS Med 7(3):e1000245. doi:10.1371/journal.pmed.1000245</BibUnst
ructured>
</Citation>
<Citation ID="CR145">
<BibArticle>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Verwei</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JA</Initials>
<FamilyName>Burgsteden</FamilyName>
<Particle>van</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>CAM</Initials>
<FamilyName>Krul</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JJM</Initials>
<FamilyName>Sandt</FamilyName>
<Particle>van de</Particle>
</BibAuthorName>
<BibAuthorName>
<Initials>AP</Initials>
<FamilyName>Freidig</FamilyName>
</BibAuthorName>
<Year>2006</Year>
<ArticleTitle Language="En">Prediction of in vivo embryotoxic effect levels with
a combination of in vitro studies and PBPK modelling</ArticleTitle>
<JournalTitle>Toxicol Lett</JournalTitle>
<VolumeID>165</VolumeID>
<IssueID>1</IssueID>
<FirstPage>79</FirstPage>
<LastPage>87</LastPage>
<BibArticleDOI>10.1016/j.toxlet.2006.01.017</BibArticleDOI>
</BibArticle>
<BibUnstructured>Verwei M, van Burgsteden JA, Krul CAM, van de Sandt JJM, Freidi
g AP (2006) Prediction of in vivo embryotoxic effect levels with a combination o
f in vitro studies and PBPK modelling. Toxicol Lett 165(1):79–87. doi:10.
1016/j.toxlet.2006.01.017</BibUnstructured>
</Citation>
<Citation ID="CR146">
<BibArticle>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Viswanathan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Chirasatitsin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Ngamkham</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>AJ</Initials>
<FamilyName>Engler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Battaglia</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Cell instructive microporous scaffolds through inter
face engineering</ArticleTitle>
<JournalTitle>J Am Chem Soc</JournalTitle>
<VolumeID>134</VolumeID>
<IssueID>49</IssueID>
<FirstPage>20103</FirstPage>
<LastPage>20109</LastPage>
<BibArticleDOI>10.1021/ja308523f</BibArticleDOI>
</BibArticle>
<BibUnstructured>Viswanathan P, Chirasatitsin S, Ngamkham K, Engler AJ, Battagli
a G (2012) Cell instructive microporous scaffolds through interface engineering.
J Am Chem Soc 134(49):20103–20109. doi:10.1021/ja308523f</BibUnstructure
d>
</Citation>
<Citation ID="CR147">
<BibArticle>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Viswanathan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Gaskell</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Moens</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>OJ</Initials>
<FamilyName>Culley</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Hansen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MKR</Initials>
<FamilyName>Gervasio</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>YJ</Initials>
<FamilyName>Yeap</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Danovi</FamilyName>
</BibAuthorName>
<Year>2014</Year>
<ArticleTitle Language="En">Human pluripotent stem cells on artificial microenvi
ronments: a high content perspective</ArticleTitle>
<JournalTitle>Front Pharmacol</JournalTitle>
<VolumeID>5</VolumeID>
<FirstPage>150</FirstPage>
<BibArticleDOI>10.3389/fphar.2014.00150</BibArticleDOI>
</BibArticle>
<BibUnstructured>Viswanathan P, Gaskell T, Moens N, Culley OJ, Hansen D, Gervasi
o MKR, Yeap YJ, Danovi D (2014) Human pluripotent stem cells on artificial micro
environments: a high content perspective. Front Pharmacol 5:150. doi:10.3389/fph
ar.2014.00150</BibUnstructured>
</Citation>
<Citation ID="CR148">
<BibArticle>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Watanabe</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Ueno</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>D</Initials>
<FamilyName>Kamiya</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Nishiyama</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Matsumura</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Wataya</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JB</Initials>
<FamilyName>Takahashi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Nishikawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Nishikawa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Muguruma</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>Y</Initials>
<FamilyName>Sasai</FamilyName>
</BibAuthorName>
<Year>2007</Year>
<ArticleTitle Language="En">A ROCK inhibitor permits survival of dissociated hum
an embryonic stem cells</ArticleTitle>
<JournalTitle>Nat Biotechnol</JournalTitle>
<VolumeID>25</VolumeID>
<IssueID>6</IssueID>
<FirstPage>681</FirstPage>
<LastPage>686</LastPage>
<BibArticleDOI>10.1038/nbt1310</BibArticleDOI>
</BibArticle>
<BibUnstructured>Watanabe K, Ueno M, Kamiya D, Nishiyama A, Matsumura M, Wataya
T, Takahashi JB, Nishikawa S, Nishikawa S, Muguruma K, Sasai Y (2007) A ROCK inh
ibitor permits survival of dissociated human embryonic stem cells. Nat Biotechno
l 25(6):681–686. doi:10.1038/nbt1310</BibUnstructured>
</Citation>
<Citation ID="CR149">
<BibArticle>
<BibAuthorName>
<Initials>SL</Initials>
<FamilyName>Wenger</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>JR</Initials>
<FamilyName>Senft</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LM</Initials>
<FamilyName>Sargent</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>R</Initials>
<FamilyName>Bamezai</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>N</Initials>
<FamilyName>Bairwa</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SG</Initials>
<FamilyName>Grant</FamilyName>
</BibAuthorName>
<Year>2004</Year>
<ArticleTitle Language="En">Comparison of established cell lines at different pa
ssages by karyotype and comparative genomic hybridization</ArticleTitle>
<JournalTitle>Biosci Rep</JournalTitle>
<VolumeID>24</VolumeID>
<IssueID>6</IssueID>
<FirstPage>631</FirstPage>
<LastPage>639</LastPage>
<BibArticleDOI>10.1007/s10540-005-2797-5</BibArticleDOI>
</BibArticle>
<BibUnstructured>Wenger SL, Senft JR, Sargent LM, Bamezai R, Bairwa N, Grant SG
(2004) Comparison of established cell lines at different passages by karyotype a
nd comparative genomic hybridization. Biosci Rep 24(6):631–639. doi:10.10
07/s10540-005-2797-5</BibUnstructured>
</Citation>
<Citation ID="CR150">
<BibArticle>
<BibAuthorName>
<Initials>LA</Initials>
<FamilyName>Williams</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>BN</Initials>
<FamilyName>Davis-Dusenbery</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KC</Initials>
<FamilyName>Eggan</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">SnapShot: directed differentiation of pluripotent st
em cells</ArticleTitle>
<JournalTitle>Cell</JournalTitle>
<VolumeID>149</VolumeID>
<IssueID>5</IssueID>
<FirstPage>1174</FirstPage>
<LastPage>1174.e1</LastPage>
<BibArticleDOI>10.1016/j.cell.2012.05.015</BibArticleDOI>
</BibArticle>
<BibUnstructured>Williams LA, Davis-Dusenbery BN, Eggan KC (2012) SnapShot: dire
cted differentiation of pluripotent stem cells. Cell 149(5):1174–1174.e1.
doi:10.1016/j.cell.2012.05.015</BibUnstructured>
</Citation>
<Citation ID="CR151">
<BibArticle>
<BibAuthorName>
<Initials>KF</Initials>
<FamilyName>Winklhofer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Tatzelt</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Haass</FamilyName>
</BibAuthorName>
<Year>2008</Year>
<ArticleTitle Language="En">The two faces of protein misfolding: gain- and lossof-function in neurodegenerative diseases</ArticleTitle>
<JournalTitle>EMBO J</JournalTitle>
<VolumeID>27</VolumeID>
<IssueID>2</IssueID>
<FirstPage>336</FirstPage>
<LastPage>349</LastPage>
<BibArticleDOI>10.1038/sj.emboj.7601930</BibArticleDOI>
</BibArticle>
<BibUnstructured>Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of prote
in misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J
27(2):336–349. doi:10.1038/sj.emboj.7601930</BibUnstructured>
</Citation>
<Citation ID="CR152">
<BibArticle>
<BibAuthorName>
<Initials>AM</Initials>
<FamilyName>Wobus</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>P</Initials>
<FamilyName>Löser</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Present state and future perspectives of using pluri
potent stem cells in toxicology research</ArticleTitle>
<JournalTitle>Arch Toxicol</JournalTitle>
<VolumeID>85</VolumeID>
<IssueID>2</IssueID>
<FirstPage>79</FirstPage>
<LastPage>117</LastPage>
<BibArticleDOI>10.1007/s00204-010-0641-6</BibArticleDOI>
</BibArticle>
<BibUnstructured>Wobus AM, Löser P (2011) Present state and future perspe
ctives of using pluripotent stem cells in toxicology research. Arch Toxicol 85(2
):79–117. doi:10.1007/s00204-010-0641-6</BibUnstructured>
</Citation>
<Citation ID="CR153">
<BibArticle>
<BibAuthorName>
<Initials>AM</Initials>
<FamilyName>Wobus</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Wallukat</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hescheler</FamilyName>
</BibAuthorName>
<Year>1991</Year>
<ArticleTitle Language="En">Pluripotent mouse embryonic stem cells are able to d
ifferentiate into cardiomyocytes expressing chronotropic responses to adrenergic
and cholinergic agents and Ca<Superscript>2+</Superscript> channel blockers</Ar
ticleTitle>
<JournalTitle>Differentiation</JournalTitle>
<VolumeID>48</VolumeID>
<IssueID>3</IssueID>
<FirstPage>173</FirstPage>
<LastPage>182</LastPage>
</BibArticle>
<BibUnstructured>Wobus AM, Wallukat G, Hescheler J (1991) Pluripotent mouse embr
yonic stem cells are able to differentiate into cardiomyocytes expressing chrono
tropic responses to adrenergic and cholinergic agents and Ca<Superscript>2+</Sup
erscript> channel blockers. Differentiation 48(3):173–182</BibUnstructure
d>
</Citation>
<Citation ID="CR154">
<BibArticle>
<BibAuthorName>
<Initials>AM</Initials>
<FamilyName>Wobus</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Rohwedel</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Maltsev</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Hescheler</FamilyName>
</BibAuthorName>
<Year>1994</Year>
<ArticleTitle Language="En">In vitro differentiation of embryonic stem cells int
o cardiomyocytes or skeletal muscle cells is specifically modulated by retinoic
acid</ArticleTitle>
<JournalTitle>Roux Arch Dev Biol</JournalTitle>
<VolumeID>204</VolumeID>
<IssueID>1</IssueID>
<FirstPage>36</FirstPage>
<LastPage>45</LastPage>
<BibArticleDOI>10.1007/BF00744871</BibArticleDOI>
</BibArticle>
<BibUnstructured>Wobus AM, Rohwedel J, Maltsev V, Hescheler J (1994) In vitro di
fferentiation of embryonic stem cells into cardiomyocytes or skeletal muscle cel
ls is specifically modulated by retinoic acid. Roux Arch Dev Biol 204(1):36 
13;45. doi:10.1007/BF00744871</BibUnstructured>
</Citation>
<Citation ID="CR155">
<BibArticle>
<BibAuthorName>
<Initials>MA</Initials>
<FamilyName>Young</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DE</Initials>
<FamilyName>Larson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>C</Initials>
<FamilyName>Sun</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>DR</Initials>
<FamilyName>George</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Ding</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>CA</Initials>
<FamilyName>Miller</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Lin</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>KM</Initials>
<FamilyName>Pawlik</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Chen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>X</Initials>
<FamilyName>Fan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Schmidt</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Kalicki-Veizer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>LL</Initials>
<FamilyName>Cook</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>GW</Initials>
<FamilyName>Swift</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RT</Initials>
<FamilyName>Demeter</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MC</Initials>
<FamilyName>Wendl</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MS</Initials>
<FamilyName>Sands</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>ER</Initials>
<FamilyName>Mardis</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>RK</Initials>
<FamilyName>Wilson</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TM</Initials>
<FamilyName>Townes</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>TJ</Initials>
<FamilyName>Ley</FamilyName>
</BibAuthorName>
<Year>2012</Year>
<ArticleTitle Language="En">Background mutations in parental cells account for m
ost of the genetic heterogeneity of induced pluripotent stem cells</ArticleTitle
>
<JournalTitle>Cell Stem Cell</JournalTitle>
<VolumeID>10</VolumeID>
<IssueID>5</IssueID>
<FirstPage>570</FirstPage>
<LastPage>582</LastPage>
<BibArticleDOI>10.1016/j.stem.2012.03.002</BibArticleDOI>
</BibArticle>
<BibUnstructured>Young MA, Larson DE, Sun C, George DR, Ding L, Miller CA, Lin L
, Pawlik KM, Chen K, Fan X, Schmidt H, Kalicki-Veizer J, Cook LL, Swift GW, Deme
ter RT, Wendl MC, Sands MS, Mardis ER, Wilson RK, Townes TM, Ley TJ (2012) Backg
round mutations in parental cells account for most of the genetic heterogeneity
of induced pluripotent stem cells. Cell Stem Cell 10(5):570–582. doi:10.1
016/j.stem.2012.03.002</BibUnstructured>
</Citation>
<Citation ID="CR156">
<BibArticle>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Zachar</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SM</Initials>
<FamilyName>Prasad</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SC</Initials>
<FamilyName>Weli</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>A</Initials>
<FamilyName>Gabrielsen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>K</Initials>
<FamilyName>Petersen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>MB</Initials>
<FamilyName>Petersen</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>T</Initials>
<FamilyName>Fink</FamilyName>
</BibAuthorName>
<Year>2010</Year>
<ArticleTitle Language="En">The effect of human embryonic stem cells (hESCs) lon
g-term normoxic and hypoxic cultures on the maintenance of pluripotency</Article
Title>
<JournalTitle>In Vitro Cell Dev Biol Anim</JournalTitle>
<VolumeID>46</VolumeID>
<IssueID>3–4</IssueID>
<FirstPage>276</FirstPage>
<LastPage>283</LastPage>
<BibArticleDOI>10.1007/s11626-010-9305-3</BibArticleDOI>
</BibArticle>
<BibUnstructured>Zachar V, Prasad SM, Weli SC, Gabrielsen A, Petersen K, Peterse
n MB, Fink T (2010) The effect of human embryonic stem cells (hESCs) long-term n
ormoxic and hypoxic cultures on the maintenance of pluripotency. In Vitro Cell D
ev Biol Anim 46(3–4):276–283. doi:10.1007/s11626-010-9305-3</BibUn
structured>
</Citation>
<Citation ID="CR157">
<BibArticle>
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Zimmer</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Schildknecht</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>PB</Initials>
<FamilyName>Kuegler</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>V</Initials>
<FamilyName>Tanavde</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>S</Initials>
<FamilyName>Kadereit</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>M</Initials>
<FamilyName>Leist</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Sensitivity of dopaminergic neuron differentiation f
rom stem cells to chronic low-dose methylmercury exposure</ArticleTitle>
<JournalTitle>Toxicol Sci</JournalTitle>
<VolumeID>121</VolumeID>
<IssueID>2</IssueID>
<FirstPage>357</FirstPage>
<LastPage>367</LastPage>
<BibArticleDOI>10.1093/toxsci/kfr054</BibArticleDOI>
</BibArticle>
<BibUnstructured>Zimmer B, Schildknecht S, Kuegler PB, Tanavde V, Kadereit S, Le
ist M (2011) Sensitivity of dopaminergic neuron differentiation from stem cells
<BibAuthorName>
<Initials>B</Initials>
<FamilyName>Chou</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>U</Initials>
<FamilyName>Choi</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>J</Initials>
<FamilyName>Pan</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>H</Initials>
<FamilyName>Wang</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>SN</Initials>
<FamilyName>Dowey</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>L</Initials>
<FamilyName>Cheng</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HL</Initials>
<FamilyName>Malech</FamilyName>
</BibAuthorName>
<Year>2011</Year>
<ArticleTitle Language="En">Oxidase-deficient neutrophils from X-linked chronic
granulomatous disease iPS cells: functional correction by zinc finger nuclease-m
ediated safe harbor targeting</ArticleTitle>
<JournalTitle>Blood</JournalTitle>
<VolumeID>117</VolumeID>
<IssueID>21</IssueID>
<FirstPage>5561</FirstPage>
<LastPage>5572</LastPage>
<BibArticleDOI>10.1182/blood-2010-12-328161</BibArticleDOI>
</BibArticle>
<BibUnstructured>Zou J, Sweeney CL, Chou B, Choi U, Pan J, Wang H, Dowey SN, Che
ng L, Malech HL (2011) Oxidase-deficient neutrophils from X-linked chronic granu
lomatous disease iPS cells: functional correction by zinc finger nuclease-mediat
ed safe harbor targeting. Blood 117(21):5561–5572. doi:10.1182/blood-2010
-12-328161</BibUnstructured>
</Citation>
<Citation ID="CR160">
<BibArticle>
<BibAuthorName>
<Initials>NI</Initials>
<FamilyName>zur Nieden</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>G</Initials>
<FamilyName>Kempka</FamilyName>
</BibAuthorName>
<BibAuthorName>
<Initials>HJ</Initials>
<FamilyName>Ahr</FamilyName>
</BibAuthorName>
<Year>2004</Year>