Bone marrow
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Bone marrow is a semi-solid
tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubitata'', a species of geometer mot ...
found within the spongy (also known as cancellous) portions of
bone A bone is a Stiffness, rigid tissue (anatomy), tissue that constitutes part of the vertebrate skeleton in animals. Bones protect the various organs of the body, produce red blood cell, red and white blood cells, store minerals, provide structur ...
s. In birds and mammals, bone marrow is the primary site of new
blood cell A blood cell, also called a hematopoietic cell, hemocyte, or hematocyte, is a cell produced through hematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) ...
production (or
haematopoiesis Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood Blood is a body fluid in humans and other animals that delivers necessary substances suc ...

haematopoiesis
). It is composed of hematopoietic cells,
marrow adipose tissue Marrow adipose tissue (MAT), also known as bone marrow adipose tissue (BMAT), is a type of fat deposit in bone marrow Bone marrow is a semi-solid tissue found within the spongy or cancellous portions of bone A bone is a Stiffness, rigid ti ...
, and supportive
stromal cell Stromal cells, or mesenchymal stromal cells, are differentiating cells found in abundance within bone marrow but can also be seen all around the body. Stromal cells can become connective tissue cells of any Organ (biology), organ, for example in the ...
s. In adult humans, bone marrow is primarily located in the
ribs The rib cage is the arrangement of ribs attached to the vertebral column and sternum in the thorax of most vertebrates that encloses and protects the vital organs such as the heart, lungs and great vessels. In humans, the rib cage and the sternum ...

ribs
,
vertebra In the vertebrate spinal column, each vertebra is an irregular bone with a complex structure composed of bone and some hyaline cartilage, the proportions of which vary according to the segment of the backbone and the species of vertebrate. ...
e,
sternum The sternum or breastbone is a long flat bone located in the central part of the chest. It connects to the ribs via cartilage and forms the front of the rib cage, thus helping to protect the heart, human lung, lungs, and major blood vessels from in ...

sternum
, and
bones of the pelvis A bone is a rigid tissue that constitutes part of the vertebrate skeleton in animals. Bones protect the various organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, and enable ...

bones of the pelvis
. 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. Human marrow produces approximately 500 billion blood cells per day, which join the
systemic circulation The circulatory system, also called the cardiovascular system or the vascular system, is an organ system An organ system is a group of organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many o ...
via permeable
vasculature The circulatory system, also called the cardiovascular system or the vascular system, is an organ system that permits blood to circulate and transport nutrients (such as amino acids and electrolytes), oxygen Oxygen is the chemical e ...
sinusoids A capillary is a small blood vessel The blood vessels are the components of the circulatory system that transport blood throughout the human body. These vessels transport blood cells, nutrients, and oxygen to the tissues of the body. They also ...
within the
medullary cavity The medullary cavity (''medulla'', innermost part) is the central cavity of bone A bone is a Stiffness, rigid tissue (anatomy), tissue that constitutes part of the skeleton in most vertebrate animals. Bones protect the various organs of the bo ...
. All types of hematopoietic cells, including both
myeloid Myeloid tissue, in the bone marrow sense of the word '' myeloid'' ('' myelo-'' + '' -oid''), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (''myelo-'' + '' -genous'') is any tissue of ...
and
lymphoid lineages
lymphoid lineages
, are created in bone marrow; however, lymphoid cells must migrate to other
lymphoid organs
lymphoid organs
(e.g.
thymus The thymus is a specialized primary Lymphatic system#Structure, lymphoid organ of the immune system. Within the thymus, T cell, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body ada ...

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 Cancer is a group of diseases A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not due to any immediate external injury. Diseases are often kn ...

cancer
such as
leukemia Leukemia ( also spelled leukaemia and pronounced ), is a group of blood cancer Tumors of the hematopoietic and lymphoid tissues (American English American English (AmE, AE, AmEng, USEng, en-US), sometimes called United States English or ...

leukemia
. Several types of stem cells are related to bone marrow.
Hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. This process occurs in the red bone marrow, in the core of most bones. In embryonic development, the red bone marro ...

Hematopoietic stem cell
s in the bone marrow can give rise to hematopoietic lineage cells, and
mesenchymal stem cell Mesenchymal stem cells (MSCs) also known as mesenchymal stromal cells or medicinal signaling cells are multipotent stromal cells that can Cellular differentiation, differentiate into a variety of cell types, including osteoblasts (bone cells), c ...

mesenchymal stem cell
s, which can be isolated from the primary culture of bone marrow stroma, can give rise to
bone A bone is a Stiffness, rigid tissue (anatomy), tissue that constitutes part of the vertebrate skeleton in animals. Bones protect the various organs of the body, produce red blood cell, red and white blood cells, store minerals, provide structur ...
,
adipose Adipose tissue, body fat, or simply fat is a loose connective tissue Connective tissue is one of the four basic types of animal tissue (biology), tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesod ...

adipose
, and
cartilage Cartilage (cartilaginous tissue) is a resilient and smooth elastic tissue Elastic fibers (or yellow fibers) are an essential component of the extracellular matrix In biology Biology is the natural science that studies life and living org ...

cartilage
tissue.


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 ( la, medulla ossium rubra, la, medulla ossium flava, respectively) depending on the prevalence of hematopoietic cells vs
fat cells Adipocytes, also known as lipocytes and fat cells, are the cell (biology), cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through ad ...

fat cells
. While the precise mechanisms underlying marrow regulation are not understood, compositional changes occur according to stereotypical patterns. For example, a newborn baby's bones exclusively contain hematopoietically active "red" marrow, and there is a progressive conversion towards "yellow" marrow with age. In adults, red marrow is found mainly in the central skeleton, such as the
pelvis The pelvis (plural pelves or pelvises) is the lower part of the trunk, between the abdomen The abdomen (colloquially called the belly, tummy, midriff or stomach) is the part of the body between the thorax (chest) and pelvis, in humans and in o ...

pelvis
,
sternum The sternum or breastbone is a long flat bone located in the central part of the chest. It connects to the ribs via cartilage and forms the front of the rib cage, thus helping to protect the heart, human lung, lungs, and major blood vessels from in ...
,
cranium The skull is a bone A bone is a Stiffness, rigid tissue (anatomy), tissue that constitutes part of the vertebrate skeleton in animals. Bones protect the various organs of the body, produce red blood cell, red and white blood cells, store mi ...

cranium
,
ribs The rib cage is the arrangement of ribs attached to the vertebral column and sternum in the thorax of most vertebrates that encloses and protects the vital organs such as the heart, lungs and great vessels. In humans, the rib cage and the sternum ...

ribs
,
vertebrae In the vertebrate spinal column, each vertebra (plural vertebrae) is an irregular bone with a complex structure composed of bone and some hyaline cartilage, the proportions of which vary according to the segment of the vertebral column, backbone ...

vertebrae
and
scapulae In anatomy, the scapula (plural scapulae or scapulas), also known as the shoulder bone, shoulder blade, wing bone or blade bone, is the bone that connects the humerus (upper arm bone) with the clavicle (collar bone). Like their connected bones, t ...
, and variably found in the proximal epiphyseal ends of
long bones The long bones are those that are longer than they are wide. They are one of five types of bone A bone is a Stiffness, rigid tissue (anatomy), tissue that constitutes part of the vertebrate skeleton in animals. Bones protect the various organs ...
such as the
femur The femur (; ), or thigh bone, is the proximal Standard anatomical terms of location deal unambiguously with the anatomy of animals, including humans. Terms used generally derive from Latin or Greek language, Greek roots and used to describe so ...

femur
and
humerus The humerus (; ) is a long bone in the arm that runs from the shoulder to the elbow. It connects the scapula and the two bones of the lower arm, the radius (bone), radius and ulna, and consists of three sections. The humeral upper extremity of hu ...

humerus
. In circumstances of chronic hypoxia, the body can convert yellow marrow back to red marrow to increase blood cell production.


Hematopoietic components

230px, Hematopoietic precursor cells: promyelocyte_in_the_center,_two_metamyelocytes_next_to_it_and_band_cell.html" ;"title="metamyelocyte.html" ;"title="promyelocyte in the center, two metamyelocyte">promyelocyte in the center, two metamyelocytes next to it and band cell">metamyelocyte.html" ;"title="promyelocyte in the center, two metamyelocyte">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. Marrow contains pluripotential hematopoietic stem cell, hematopoietic stem cells which give rise to the three classes of blood cells that are found in circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets (thrombocytes).


Stroma

The Stromal cell, stroma of the bone marrow includes all tissue not directly involved in the marrow's primary function of hematopoiesis. Stromal cells may be indirectly involved in hematopoiesis, providing a microenvironment that influences the function and differentiation of hematopoietic cells. For instance, they generate colony stimulating factors, which have a significant effect on hematopoiesis. Cell types that constitute the bone marrow stroma include: * fibroblasts (reticular connective tissue) * macrophages, which contribute especially to red blood cell production, as they deliver iron for hemoglobin production. * Marrow Adipose Tissue, adipocytes (fat cells) * osteoblasts (synthesize bone) * osteoclasts (resorb bone) * endothelial cells, which form the sinusoid blood vessel, sinusoids. These derive from endothelial stem cells, which are also present in the bone marrow.


Function


Mesenchymal stem cells

The bone marrow stroma contains mesenchymal stem cells (MSCs), which are also known as marrow stromal cells. These are multipotent stem cells that can Cellular differentiation, differentiate into a variety of cell types. MSCs have been shown to differentiate, in vitro or in vivo, into osteoblasts, chondrocytes, myocytes, Marrow Adipose Tissue, marrow adipocytes and Beta cell, beta-pancreatic islets cells.


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.
Hematopoietic stem cell Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. This process occurs in the red bone marrow, in the core of most bones. In embryonic development, the red bone marro ...

Hematopoietic stem cell
s may also cross the bone marrow barrier, and may thus be harvested from blood.


Lymphatic role

The red bone marrow is a key element of the lymphatic system, being one of the Lymphatic system#Primary lymphoid organs, primary lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells.The Lymphatic System
Allonhealth.com. Retrieved 5 December 2011.
The bone marrow and
thymus The thymus is a specialized primary Lymphatic system#Structure, lymphoid organ of the immune system. Within the thymus, T cell, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body ada ...

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.


Compartmentalization

Cellular compartment, 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 chemical precursor, precursors tend to gather around blood vessels, while granulocytes gather at the borders of the bone marrow.


As food

Animal bone marrow has been Bone marrow (food), used in cuisine worldwide for millennia, such as the famed Milanese Ossobuco.


Clinical significance


Disease

The normal bone marrow architecture can be damaged or displaced by aplastic anemia, cancer, 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 Leukemia ( also spelled leukaemia and pronounced ), is a group of blood cancer Tumors of the hematopoietic and lymphoid tissues (American English American English (AmE, AE, AmEng, USEng, en-US), sometimes called United States English or ...

leukemia
, which attacks its hematologic progenitor cells. Furthermore, exposure to ionizing radiation, radiation 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 poisoning 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 the iliac crest, crest of the ilium under general or local anesthesia.


Application of stem cells in therapeutics

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


Imaging

Medical imaging may provide a limited amount of information regarding bone marrow. Radiograph, Plain film x-rays pass through soft tissues such as marrow and do not provide visualization, although any changes in the structure of the associated bone may be detected. Computed tomography, 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. Magnetic resonance imaging, MRI is more sensitive and specific for assessing bone composition. MRI enables assessment of the average molecular composition of soft tissues and thus provides information regarding the relative fat content of marrow. In adult humans, "yellow" fatty marrow is the dominant tissue in bones, particularly in the (peripheral) appendicular skeleton. Because fat molecules have a high T1-weighted MRI, 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. 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. Fatty marrow change, the inverse of red marrow hyperplasia, can occur with normal aging, though it can also be seen with certain treatments such as radiation therapy. Diffuse marrow T1 hypointensity without contrast enhancement or cortical discontinuity suggests red marrow conversion or myelofibrosis. Falsely normal marrow on T1 can be seen with diffuse multiple myeloma or leukemia, 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.


Histology

ed bone marrow aspirate smear from a patient with
leukemia Leukemia ( also spelled leukaemia and pronounced ), is a group of blood cancer Tumors of the hematopoietic and lymphoid tissues (American English American English (AmE, AE, AmEng, USEng, en-US), sometimes called United States English or ...

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 Venipuncture, 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. The ratio between Myeloid cell, 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.


Donation and transplantation

Image:Bone marrow biopsy.jpg, A bone marrow harvest in progress. In a Hematopoietic stem cell transplantation, 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 radiotherapy, radiation, and then the new stem cells are introduced. Before radiation therapy or chemotherapy in cases of
cancer Cancer is a group of diseases A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not due to any immediate external injury. Diseases are often kn ...

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. Bone marrow stem cells can be induced to become neural cells to treat neurological illnesses, and can also potentially be used for the treatment of other illnesses, such as inflammatory bowel disease. In 2013, following a clinical trial, scientists proposed that bone marrow transplantation could be used to treat HIV in conjunction with antiretroviral drugs; however, it was later found that HIV remained in the bodies of the test subjects.


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 surgery, outpatient procedure, or can require 1–2 days of recovery in the hospital. Another option is to administer certain drugs that stimulate the release of stem cells from the bone marrow into circulating blood. An Intravenous therapy, intravenous Peripheral venous catheter, catheter is inserted into the donor's arm, and the stem cells are then filtered out of the blood. This procedure is similar to that used in blood or platelet donation. In adults, bone marrow may also be taken from the
sternum The sternum or breastbone is a long flat bone located in the central part of the chest. It connects to the ribs via cartilage and forms the front of the rib cage, thus helping to protect the heart, human lung, lungs, and major blood vessels from in ...
, while the tibia is often used when taking samples from infants. In newborns, stem cells may be retrieved from the umbilical cord.


Fossil record

The earliest fossilised evidence of bone marrow was discovered in 2014 in ''Eusthenopteron'', a lobe-finned fish which lived during the Devonian period approximately 370 million years ago. Scientists from Uppsala University and the European Synchrotron Radiation Facility used X-ray microtomography, X-ray synchrotron microtomography to study the fossilised interior of the skeleton's
humerus The humerus (; ) is a long bone in the arm that runs from the shoulder to the elbow. It connects the scapula and the two bones of the lower arm, the radius (bone), radius and ulna, and consists of three sections. The humeral upper extremity of hu ...

humerus
, finding organised tubular structures akin to modern vertebrate bone marrow. ''Eusthenopteron'' is closely related to the early tetrapods, which ultimately evolved into the land-dwelling mammals and lizards of the present day.


See also

* National Marrow Donor Program * Gift of Life Marrow Registry


References


Further reading


''Nature Bone Marrow Transplantation''
(Nature Publishing Group) – specialist scientific journal with articles on bone marrow biology and clinical uses. * *


External links


Bone marrow histology photomicrographs

Haploidentical Bone Marrow Transplants: Truths & Myths
{{DEFAULTSORT:Bone Marrow Bone marrow, Hematopoiesis Endocrine system Lymphoid organ Lymphatic system Skeletal system Stem cells