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StemCells:Introductionand

ProspectsinMedicine
www.gothamgazette.com/.../stemcell/stem_cell.jpg
Overview
Settingthestageforthediscussion:historical
perspectiveandprospectsinregenerative
medicine
StemCellBasics:
Whatarestemcells?
Wheredostemcellscomefrom?
StemCellAdvancesintheNews!
StemCellResearchChallenges
HistoricalPerspectiveand
ProspectsforRegenerative
Medicine
HistoricalPerspectives
Majorchangesinregenerativemedicine
(replacementofdamagedordiseasedcellsand
tissueswithnewcellsandtissues)duetoadvancesin
stemcelltechnologies
Somestemcelltherapiesinexistenceforover50
years.Firstsuccessfulbonemarrowtransplantdone
in1956onleukemiapatient.Bonemarrowcontains
adultderived hematopoieticstemcells(ableto
regeneratetissuessimilartothespecializedtissuesin
whichtheyarefound.
Embryonicstemcellsbelievedtohavegreater
potential.Thislineofstemcellresearchhasbeen
themostcontroversial.
From Solter, D. 2006 Nature Reviews Genetics 7, 319-327.
2007NobelPrizeinMedicine
MarioR.Capecchi,MartinJ.Evans andOliver
Smithies fortheirdiscoveriesof theprinciples
forintroducingspecificgenemodificationsin
micebytheuseofembryonicstemcells.
STEMCELLBASICS
I.Whatarestemcells?
BasicCharacteristicsofStemCells
Whatarethe
SIGNALS???
AdaptedfromStemCellsandCloningbyKellyA.Hogan;
Howdocellsremain
selfrenewingand
unspecialized?
Hormones
Growthfactors
Smallproteins
Remember:
Unlikegametes(eggandspermcells),allother
cells(somaticcells)havethesameDNAcontent
andthesamegenes.
SinceDNA RNA protein,thenhowcanwe
accountfordifferentproteinpatternsindifferent
typesofcells?
Theexpressionpatternofgeneswithin
differenttypesofcellsisNOTidentical.
ProteinProfilesinDifferentCellTypes
FigurefromStemCellsandCloningbyK.A.Hogan
Allstemcellsarenotalike!
Somestemcellshavemorepotentialthanothers.
POTENCY describesthisflexibility.
Unipotent stemcellsformonlyonetypeof
specializedcelltype.
Multipotent stemcellscanformmultipletypesof
cellsandtissuetypes.
Pluripotent stemcellscanformmostorallcell
typesintheadult.
Totipotent stemcellscanformalladultcelltypes
aswellasthespecializedtissuestosupport
developmentoftheembryo(e.g.,theplacenta)
STEMCELLBASICS
II.Wheredostemcellscomefrom?
Sourcesofstemcellsduringdevelopment
ad
AdaptedfromStemCellsandCloningbyK.A.Hogan
[P]
[P] = pluripotent
[M] = multipotent
[T] = totipotent
[T]
[P or M]
[P or M]
[P]
Teratomas (benign);
Teratocarcinomas
(malignant).
[P]
OriginofHumanEmbryonicStemCells
IsolationofHumanEmbryonicStemCells
FigurefromStemCellsandCloningbyK.A.Hogan
FirstdonebyDr.
JamesThompson
andcolleaguesat
theUniversityof
Wisconsin(1998).
http://creationwiki.org/index.php/Stem_cell
PropertiesofHumanEmbryonicStem
CellsinCulture
Pluripotent abletoformanyof~200different
typesofcellsofthebody
Selfrenewing invitro canpropagateor
proliferateindefinitelyintheundifferentiated
state
Express theenzymetelomerase (requiredto
maintaintheendsofchromosomes)and Oct4 (a
masterregulatorofESCpluripotency)
Maintainnormalchromosomestructureand
complement evenafterlongperiodsinculture
(unlikemanyothertissueculturecelllines)
StemCellResearchintheNews!
SelectedNewsaboutStemCells
ScientistsFindWaytoTrackStemCellsinBrain
(Science, November2007)
StemCellsRestoreMemoryinMice
(JournalofNeuroscience, October2007)
ResearchersIsolateAdultStemCellsforFirstTimeinTendon
(NatureMedicine,September2007)
StemCellsFromTestesProduceWideRangeofTissueTypes
(Nature, September2007)
ScientistsTurnHumanSkinCellsintoStemCells
(Science;Cell,November2007)
FirstNeuronsCreatedfromALSPatientsSkinCells
(Science,July2008[online])
ScientistsTurnHumanSkinCellsinto
StemCells
IMPACT:
Understandingbirthdefects
Possibilityofgeneratingpatientspecificstem
celllinestostudythemechanismofdifferent
diseasesinthelaboratory
Creationofmodelsfordrugdiscoveryand
testingthetoxiceffectsofdrugs
Tissueengineering(e.g.,useofprogenitor
cellstomakeartificialbladders)
Doesthisalterthedebateabouttheuseof
humanEScellsornot?
ParkinsonsDisease(PD):StemCellInsights
Source cells DifferentiatedCelltype Hostanimalreceiving
braintransplant
Results
Monkey ESCs Dopamineproducing
neurons
Monkey modelofPD DiminishedPDsymptoms;
lowsurvival rateof
transplantedcells
HumanESCs Dopamineproducing
neurons
RatmodelofPD Significantlyimproved
musclecoordination;
tumorformationinbrains
Humanneuralprogenitor
cellsfromfetaltissue
engineeredtoexpressa
survivalfactor
N/A Ratandmonkey modelsof
PD
Improvedsymptomsof
PD;newdopamine
producing neurons
generated;effectsnotlong
lasting
Adult humanbrainbiopsy
cells
Neural progenitorcells Mouse Newneuronsgenerated
Mouseorhumanneural
ASCs
N/A Mousemodelofrelated
disease, Sandhoffs
disease
Increasedlifespan;
delayedlossofmotor
function;notumors
HumanESCs Neural progenitorcells Mousemodel of
Sandhoffsdisease
Increasedlifespan;
delayedlossofmotor
function;notumors
adaptedfromK.A.Hogan,StemCellsandCloning.
StemCellTherapyChallenges
EthicalconsiderationsforESCresearch
Safetychallenges UseofESCsor
differentiatedcellsderivedfromESCsfor
therapy?Considerationstoavoidtumor
formation.Immunesystemchallengesto
avoidrejectionofforeigncells.
Understandingthebasicmechanismsthat
underliestemcellbiology
Summary:
Stemcelltherapiesofferregenerativeprospectsfornumerous
humandiseases
Stemcellsarecapableofrenewalanddifferentiation.
Stemcellsarederivedfromnumeroussourcesandhave
differentpotencycapacities.
Adultstemcells(ASCs)havebeendetectedinnumeroustissues.
Considerabledebatesurroundstheuseofembryonicstemcells.
Adultstemcellsmayoffersimilarprospectsfortherapyasdoas
ESCs,yetacompleteunderstandingofstemcellapplications
willrequireabasicunderstandingofdifferentiationandrenewal
mechanismsinASCsandESCsaswell.
OdetoaStemCell,PartII
byVCW
Thereoncewasstemcellstuckinthehood
Dividingendlessly,butonlywishinghecould
Becomesomethingelse,askincell,ahaircell,orsomeothertype
Butforweekshesulkedandutteredthisgripe
WhyamInotneeded?tohisfriendshewouldsay
Isntthereacallforaspecialistsomewheretoday?
Well,ifyoureallywanttoleavetogetanewstart,
Youmustchangeyourtune,forsurelythereisanart
Toconsiderwhatsignalsyouhearandchoicesyoumake.
Divideoncemoreforthespecialjourneyyoutake.
Daretobedifferent,asyoudifferentiate!

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