Bone marrow

Source: Wikipedia, the free encyclopedia.
For bone marrow as eaten by humans, see Bone marrow (food).

Bone marrow
Hematopoietic system, Immune system,[1] Lymphatic system
Identifiers
Latinmedulla ossium
MeSHD001853
TA98A13.1.01.001
TA2388
FMA9608
Anatomical terminology]

Bone marrow is a semi-solid

marrow adipose tissue, and supportive stromal cells. In adult humans, bone marrow is primarily located in the ribs, vertebrae, sternum, and bones of the pelvis.[4] Bone marrow comprises approximately 5% of total body mass in healthy adult humans, such that a man weighing 73 kg (161 lbs) will have around 3.7 kg (8 lbs) of bone marrow.[5]

Human marrow produces approximately 500 billion blood cells per day, which join the

sinusoids within the medullary cavity.[6] All types of hematopoietic cells, including both myeloid and lymphoid lineages, are created in bone marrow; however, lymphoid cells must migrate to other lymphoid organs (e.g. thymus
) in order to complete maturation.

Bone marrow transplants can be conducted to treat severe diseases of the bone marrow, including certain forms of cancer such as leukemia. Several types of stem cells are related to bone marrow. Hematopoietic stem cells in the bone marrow can give rise to hematopoietic lineage cells, and mesenchymal stem cells, which can be isolated from the primary culture of bone marrow stroma, can give rise to bone, adipose, and cartilage tissue.[7]

Structure

The composition of marrow is dynamic, as the mixture of cellular and non-cellular components (connective tissue) shifts with age and in response to systemic factors. In humans, marrow is colloquially characterized as "red" or "yellow" marrow (

long bones such as the femur and humerus. In circumstances of chronic hypoxia, the body can convert yellow marrow back to red marrow to increase blood cell production.[9]

Hematopoietic components

See also:
Hematopoietic system
orthochromatic erythroblast marked), and megakaryocytic cells
Hematopoietic precursor cells: promyelocyte in the center, two metamyelocytes next to it and band cells from a bone marrow aspirate

At the cellular level, the main functional component of bone marrow includes the progenitor cells which are destined to mature into blood and lymphoid cells. Human marrow produces approximately 500 billion blood cells per day.

platelets (thrombocytes).[11]

Cellular constitution of the red bone marrow parenchyma[12]
Group Cell type Average
fraction		 Reference
range
Myelopoietic
cells		 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
Eosinophilic metamyelocytes
 1.2% 0.4–2.2
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
Erythropoietic
cells
Pronormoblasts
 0.6% 0.2–1.3
Basophilic normoblasts
 1.4% 0.5–2.4
Polychromatic normoblasts
 21.6% 17.9–29.2
Orthochromatic normoblast
 2.0% 0.4–4.6
Other cell
types		 Megakaryocytes < 0.1% 0.0-0.4
Plasma cells 1.3% 0.4-3.9
Reticular cells 0.3% 0.0-0.9
Lymphocytes 16.2% 11.1-23.2
Monocytes 0.3% 0.0-0.8

Stroma

The

colony stimulating factors
, which have a significant effect on hematopoiesis. Cell types that constitute the bone marrow stroma include:

Function

Central hematopoietic and antigen-responsive organ

That bone marrow is a priming site for T-cell responses to blood-borne antigens was first described in 2003.[13] Mature circulating naïve T cells home to bone marrow sinuses after they have passed through arteries and arterioles.[14] They transmigrate sinus endothelium and enter the parenchyma which contains dendritic cells (DCs). These have a capacity of antigen uptake, processing, and presentation.[13] Cognate interactions between antigen-specific T cells and antigen-presenting DCs (APCs) in parenchyma lead to rapid T-APC cluster formation followed by T cell activation, T cell proliferation and T cell re-circulation to blood.[13] These findings were corroborated and extended in 2013 by in situ two-photon dynamic imaging of mice skulls.[15]

Importance for storage and long-term survival of memory B and memory T cells

Bone marrow is a nest for migratory memory T cells[16] and a sanctuary for plasma cells.[17] This has implications for adaptive immunity and vaccinology.[17] Memory B and T cells persist in the parenchyma in dedicated survival niches organized by stromal cells.[18] This memory can be maintained over long time periods in the form of quiescent cells[18] or by repeated antigenic restimulation.[19] Bone marrow protects and optimizes immunological memory during dietary restriction.[20] In cancer patients, cancer-reactive memory T cells can arise in bone marrow spontaneously or after specific vaccination.[21] Bone marrow is a center of a variety of immune activities: i) hematopoiesis, ii) osteogenesis, iii) immune responses, iv) distinction between self and non-self antigens, v) central immune regulatory function, vi) storage of memory cells, vii) immune surveillance of the central nervous system, viii) adaptation to energy crisis, ix) provision of mesenchymal stem cells for tissue repair. [22]

Mesenchymal stem cells

Main article: Mesenchymal stem cell

The bone marrow stroma contains

marrow adipocytes and beta-pancreatic islets cells.[citation needed
]

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, such as aquaporin and glycophorin, that are required to attach to and pass the blood vessel endothelium.[23] Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be harvested from blood.[citation needed]

Lymphatic role

The red bone marrow is a key element of the

lymphatic fluid in the lymphatic system.[citation needed
]

Compartmentalization

granulocytes gather at the borders of the bone marrow.[11]

As food

See also: Bone marrow (food)

People have used animal bone-marrow in cuisine worldwide for millennia, as in the famed Milanese Ossobuco.[25]

Clinical significance

Disease

The normal bone marrow architecture can be damaged or displaced by

radiation poisoning are due to damage sustained by the bone marrow cells.[citation needed
]

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 the crest of the ilium under general or local anesthesia.[27]

Application of stem cells in therapeutics

Bone marrow derived stem cells have a wide array of application in regenerative medicine.[28]

Imaging

Medical imaging may provide a limited amount of information regarding bone marrow.

CT imaging has somewhat better capacity for assessing the marrow cavity of bones, although with low sensitivity and specificity. For example, normal fatty "yellow" marrow in adult long bones is of low density (-30 to -100 Hounsfield units), between subcutaneous fat and soft tissue. Tissue with increased cellular composition, such as normal "red" marrow or cancer cells within the medullary cavity will measure variably higher in density.[30]

T1-relaxivity, T1-weighted imaging sequences show "yellow" fatty marrow as bright (hyperintense). Furthermore, normal fatty marrow loses signal on fat-saturation sequences, in a similar pattern to subcutaneous fat.[citation needed
]

When "yellow" fatty marrow becomes replaced by tissue with more cellular composition, this change is apparent as decreased brightness on T1-weighted sequences. Both normal "red" marrow and pathologic marrow lesions (such as cancer) are darker than "yellow" marrow on T1-weight sequences, although can often be distinguished by comparison with the MR signal intensity of adjacent soft tissues. Normal "red" marrow is typically equivalent or brighter than skeletal muscle or intervertebral disc on T1-weighted sequences.[8][31]

Fatty marrow change, the inverse of red marrow

myelofibrosis. Falsely normal marrow on T1 can be seen with diffuse multiple myeloma or leukemic infiltration when the water to fat ratio is not sufficiently altered, as may be seen with lower grade tumors or earlier in the disease process.[33]

Histology

Main article: Bone marrow 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 by phlebotomy), 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.[citation needed]

The ratio between

myelogenous leukemias, decrease in polycythemias, and reverse in cases of thalassemia.[34]

Donation and transplantation

Main article: Hematopoietic stem cell transplantation
A bone marrow harvest in progress
The preferred sites for the procedure

In a

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.[35]

Bone marrow stem cells can be induced to become neural cells to treat neurological illnesses,

antiretroviral drugs;[38][39] however, it was later found that HIV remained in the bodies of the test subjects.[40]

Harvesting

The stem cells are typically harvested directly from the red marrow in the

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.[41]

Another option is to administer certain drugs that stimulate the release of stem cells from the bone marrow into circulating blood.

sternum, while the tibia is often used when taking samples from infants.[27] In newborns, stem cells may be retrieved from the umbilical cord.[43]

Persistent viruses

Using quantitative Polymerase Chain Reaction (qPCR) and Next-generation Sequencing (NGS) a maximum of five DNA viruses per individual have been identified. Included were several herpesviruses, hepatitis B virus, Merkel cell polyomavirus, and human papillomavirus 31. Given the reactivation and/or oncogenic potential of these viruses, their repercussion on hematopoietic and malignant disorders calls for further studies.[44]

Fossil record

Bone marrow may have first evolved in Eusthenopteron, a species of prehistoric fish with close links to early tetrapods.

The earliest fossilised evidence of bone marrow was discovered in 2014 in

lobe-finned fish which lived during the Devonian period approximately 370 million years ago.[45] Scientists from Uppsala University and the European Synchrotron Radiation Facility used X-ray synchrotron microtomography to study the fossilised interior of the skeleton's humerus, finding organised tubular structures akin to modern vertebrate bone marrow.[45] Eusthenopteron is closely related to the early tetrapods, which ultimately evolved into the land-dwelling mammals and lizards of the present day.[45]

See also

References

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Further reading

External links

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