Bone marrow

Bone marrow

A simplified illustration of cells in bone marrow

Latin Medulla ossium

MeSH Bone+Marrow

Code TA A13.1.01.001

Bone marrow is the flexible tissue found in the interior of bones. In humans, red blood cells are produced in
the heads of long bones, in a process known as hematopoesis. On average, bone marrow constitutes 4% of
the total body mass of humans; in an adult weighing 65 kilograms (140 lb), bone marrow accounts for
approximately 2.6 kilograms (5.7 lb). The hematopoietic compartment of bone marrow produces approximately
500 billion blood cells per day, which use the bone marrow vasculature as a conduit to the body's systemic
circulation.[1] Bone marrow is also a key component of the lymphatic system, producing the lymphocytes that
support the body's immune system.[2]

Bone marrow transplants can be conducted to treat severe diseases of the bone marrow, including certain
forms of cancer. Additionally, bone marrow stem cells have been successfully transformed into
functional neural cells,[3] and can also potentially be used to treat illnesses such asinflammatory bowel
disease.[4]

Marrow types
A femoral head with a cortex of cortical bone and medulla of trabecular bone. Both red bone marrow and a focus of yellow
bone marrow are visible.

The two types of bone marrow are medulla ossium rubra (red marrow), which consists mainly
of hematopoietic tissue, and medulla ossium flava (yellow marrow), which is mainly made up of fat cells. Red
blood cells, platelets and most white blood cells arise in red marrow. Both types of bone marrow contain
numerous blood vessels and capillaries. At birth, all bone marrow is red. With age, more and more of it is
converted to the yellow type; only around half of adult bone marrow is red. Red marrow is found mainly in
the flat bones, such as the pelvis, sternum, cranium, ribs, vertebrae andscapulae, and in
the cancellous ("spongy") material at the epiphyseal ends of long bones such as the femur and humerus.
Yellow marrow is found in the medullary cavity, the hollow interior of the middle portion of long bones. In cases
of severe blood loss, the body can convert yellow marrow back to red marrow to increase blood cell production.

Stroma

The stroma of the bone marrow is all tissue not directly involved in the primary function of hematopoiesis.
Yellow bone marrow makes up the majority of bone marrow stroma, in addition to smaller concentrations of
stromal cells located in the red bone marrow. Though not as active as parenchymal red marrow, stroma is
indirectly involved in hematopoiesis, since it provides the hematopoietic microenvironment that facilitates
hematopoiesis by the parenchymal cells. For instance, they generate colony stimulating factors, which have a
significant effect on hematopoiesis. Cells that constitute the bone marrow stroma are:

 fibroblasts (reticular connective tissue)

 macrophages

 adipocytes

 osteoblasts

 osteoclasts
 endothelial cells, which form the sinusoids. These derive from endothelial stem cells, which are also
present in the bone marrow.[5]

Macrophages contribute especially to red blood cell production, as they deliver iron for hemoglobin production.

Bone marrow barrier

The blood vessels of the bone marrow constitute a barrier, inhibiting immature blood cells from leaving the
marrow. Only mature blood cells contain the membrane proteins required to attach to and pass the blood
vessel endothelium. Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be
harvested from blood.

Mesenchymal stem cells

The bone marrow stroma contains mesenchymal stem cells (MSCs),[5] also known as marrow stromal cells.
These are multipotent stem cells that can differentiate into a variety of cell types. MSCs have been shown to
differentiate, in vitro or in vivo, into osteoblasts, chondrocytes, myocytes, adipocytes and beta-pancreatic islets
cells. MSCs can also transdifferentiate into neuronal cells.[3]

Red marrow parenchyma

Cellular components

Hematopoietic precursor cells:promyelocyte in the center, twometamyelocytes next to it and band cells from a bone marrow
aspirate.

Cellular constitution of the red bone marrow parenchyma [6]

Average Reference
Group Cell type
fraction range
 Myeloblasts 0.9% 0.2-1.5

Promyelocytes 3.3% 2.1-4.1

Neutrophilic myelocytes 12.7% 8.2-15.7

Eosinophilic myelocytes 0.8% 0.2-1.3

Neutrophilic metamyelocytes 15.9% 9.6-24.6

Cells of
Eosinophilic metamyelocytes 1.2% 0.4-2.2
myelopoiesis

Neutrophilic band cells 12.4% 9.5-15.3

Eosinophilic band cells 0.9% 0.2-2.4

Segmented neutrophils 7.4% 6.0-12.0

Segmented eosinophils 0.5% 0.0-1.3

Segmented basophils and mast cells 0.1% 0.0-0.2

Pronormoblasts 0.6% 0.2-1.3

Basophilic normoblasts 1.4% 0.5-2.4

Cells of
erythropoiesis
Polychromatic normoblasts 21.6% 17.9-29.2

Orthochromatic normoblast 2.0% 0.4-4.6

 Megakaryocytes < 0.1% 0.0-0.4

Plasma cells 1.3% 0.4-3.9

Other cell types Reticular cells 0.3% 0.0-0.9

Lymphocytes 16.2% 11.1-23.2

Monocytes 0.3% 0.0-0.8

In addition, the bone marrow contains hematopoietic stem cells, which give rise to the three classes of blood
cells that are found in the circulation: white blood cells (leukocytes), red blood cells(erythrocytes),
and platelets (thrombocytes).[5]

Compartmentalization
Biological compartmentalization is evident within the bone marrow, in that certain cell types tend to aggregate
in specific areas. For instance, erythrocytes, macrophages, and their precursorstend to gather around blood
vessels, while granulocytes gather at the borders of the bone marrow.

Lymphatic role
The red bone marrow is a key element of the lymphatic system, being one of the primary lymphoid organs that
generate lymphocytes from immature hematopoietic progenitor cells.[2] The bone marrow and thymus constitute
the primary lymphoid tissues involved in the production and early selection of lymphocytes. Furthermore, bone
marrow performs a valve-like function to prevent the backflow of lymphatic fluid in the lymphatic system.

Diseases of the bone marrow

The normal bone marrow architecture can be damaged or displaced by aplastic anemia, malignancies such
as multiple myeloma, or infections such as tuberculosis, leading to a decrease in the production of blood cells
and blood platelets. The bone marrow can also be affected by various forms of leukemia, which attacks its
hematologic progenitor cells.[7] Furthermore, exposure toradiation or chemotherapy will kill many of the rapidly
dividing cells of the bone marrow, and will therefore result in a depressed immune system. Many of the
symptoms of radiation sickness are due to damage sustained by the bone marrow cells.
To diagnose diseases involving the bone marrow, a bone marrow aspiration is sometimes performed. This
typically involves using a hollow needle to acquire a sample of red bone marrow from thecrest of the
ilium under general or local anesthesia.

Examination

A Wright's-stained bone marrow aspirate smear from a patient with leukemia.

Bone marrow examination is the pathologic analysis of samples of bone marrow obtained via biopsy and bone
marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including
leukemia, multiple myeloma, anemia, and pancytopenia. The bone marrow produces the cellular elements of
the blood, including platelets, red blood cells and white blood cells. While much information can be gleaned by
testing the blood itself (drawn from a vein byphlebotomy), it is sometimes necessary to examine the source of
the blood cells in the bone marrow to obtain more information on hematopoiesis; this is the role of bone marrow
aspiration and biopsy.

The ratio between myeloid series and erythroid cells is relevant to bone marrow function, and also to diseases
of the bone marrow and peripheral blood, such as leukemia and anemia. The normal myeloid-to-erythroid ratio
is around 3:1; this ratio may increase in myelogenous leukemias, decrease in polycythemias, and reverse in
cases of thalassemia.[8]

Donation and transplantation

A bone marrow harvest in progress.

In a bone marrow transplant, hematopoietic stem cells are removed from a person and infused into another
person (allogenic) or into the same person at a later time (autologous). If the donor and recipient are
compatible, these infused cells will then travel to the bone marrow and initiate blood cell production.
Transplantation from one person to another is conducted for the treatment of severe bone marrow diseases,
such as congenital defects, autoimmune diseases or malignancies. The patient's own marrow is first killed off
with drugs or radiation, and then the new stem cells are introduced. Before radiation therapy
or chemotherapy in cases of cancer, some of the patient's hematopoietic stem cells are sometimes harvested
and later infused back when the therapy is finished to restore the immune system. In addition, bone marrow
stem cells can be induced to become neural cells to treat neurological illnesses,[3] and can also potentially be
used for the treatment of other illnesses, such as inflammatory bowel disease.[9]

Harvesting
The stem cells are typically harvested directly from the red marrow in the iliac crest, often under general
anesthesia. The procedure is minimally invasive and does not require stitches afterwards. Depending on the
donor's health and reaction to the procedure, the actual harvesting can be an outpatient procedure, or can
require 1–2 days of recovery in the hospital.[10]

Another option is to administer certain drugs that stimulate the release of stem cells from the bone marrow into
circulating blood.[11] An IV is inserted into the donor's arm, and the stem cells are filtered out of the blood. This
procedure is similar to donating blood or platelets. In adults, bone marrow may also be taken from the sternum,
while the tibia is often used when taking samples from infants.[12] In newborns, stem cells may be retrieved from
the umbilical cord.[13]

References

1. ^ "Challenges in Cardiac Tissue Engineering"; Gordana Vunjak-Novakovic, Ph.D.,Nina Tandon, Ph.D.,

Amandine Godier, B.S.,1 Robert Maidhof, M.S.,Anna Marsano, Ph.D., Timothy P. Martens, M.D., Ph.D.,
and Milica Radisic, Ph.D. Tissue Engineering: Part B; Volume 16, Number 2 (2010).

2. ^ a b The Lymphatic System. Allonhealth.com. Retrieved 5 December 2011.

3. ^ a b c "Antibody Transforms Stem Cells Directly Into Brain Cells". Science Daily. 22 April 2013. Retrieved

24 April 2013.

4. ^ "Research Supports Promise of Cell Therapy for Bowel Disease". Wake Forest Baptist Medical Center. 28

February 2013. Retrieved 5 March 2013.

5. ^ a b c Raphael Rubin and David S. Strayer (2007). Rubin's Pathology: Clinicopathologic Foundations of
Medicine. Lippincott Williams & Wilkins. p. 90. ISBN 0-7817-9516-8.

6. ^ Appendix A:IV in Wintrobe's clinical hematology (9th edition). Philadelphia: Lea & Febiger (1993).
7. ^ "Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic

cell". Nature. 1997. Retrieved 9 November 2012.

8. ^ "Definition: 'M:E Ratio'". Stedman's Medical Dictionary via MediLexicon.com. 2006. Retrieved 20

December 2012.

9. ^ "Research Supports Promise of Cell Therapy for Bowel Disease". Wake Forest Baptist Medical Center. 28

February 2013. Retrieved 5 March 2013.

10. ^ National Marrow Donor Program Donor Guide. Marrow.org. Retrieved 5 November 2012.

11. ^ Mayo Clinic: Bone marrow donation: What to expect when you donate. Mayo Clinic. Retrieved 16

February 2013.

12. ^ "Bone Marrow Aspiration and Biopsy". Lab Tests Online UK. Retrieved 16 February 2013.

13. ^ "Production of stem cells with embryonic characteristics from human umbilical cord blood".Wiley Online

Library. 11 August 2005. Retrieved 29 January 2012.

14. ^ Bruce Bower. "Hunting ancient scavengers – some anthropologists say early humans were scavengers,

not hunters". Science News. 9 March 1985. Retrieved 16 February 2013.

15. ^ La Petite Bouche (Food Blog): Roasted Bone Marrow. 30 August 2010. Retrieved 5 December 2011.

16. ^ "Kansi". Flickr. 22 February 2010. Retrieved 26 November 2012.