Bone marrow is the spongy tissue inside some of the bones in the body, including the hip and thigh bones. Bone marrow contains immature cells, called stem cells.
Healthy bone marrow and blood cells are needed in order to live. When disease affects bone marrow so that it can no longer function effectively, a marrow or cord blood transplant could be the best treatment option; for some patients it is the only potential cure.
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Fast facts on bone marrow
Here are some key points about bone marrow. More detail and supporting information is in the main article.
- A bone marrow transplant can save the lives of people battling leukemia, lymphoma and other blood cancers.
- At birth, all bone marrow is red. As humans age, red marrow increasingly begins to convert to yellow marrow.
- In adults, around half of the bone marrow is red and half is yellow.
- 200 billion new red blood cells are made by the bone marrow every day, along with white blood cells and platelets.
- Around 1% of the body's red blood cells are regenerated every day.
- Healthy bone marrow manufactures between 150,000 and 450,000 platelets per microliter of blood, the amount of blood that fits on the head of a pin.
- Bone marrow contains mesenchymal and hematopoietic stem cells.
- Around 10,000 people in the US are diagnosed each year with diseases that require bone marrow transplants.
- 7 out of 10 people who require a bone marrow transplant do not have a matching donor in their family, and rely on the registry of bone marrow donors to find a match.
- The process for matching a patient with a donor involves comparing human leukocyte antigen (HLA) types in order to find a match.
- Several diseases, many of which are incurable, pose a threat to bone marrow and prevent bone marrow from turning stem cells into essential cells.
What is bone marrow?
Bone marrow is soft, gelatinous tissue that fills the medullary cavities - the centers of bones. There are two types of bone marrow: red bone marrow (also known as myeloid tissue) and yellow bone marrow (fatty tissue).1
Both types of bone marrow are highly vascular and enriched with numerous blood vessels and capillaries.2
The bone marrow makes more than 200 billion new blood cells every day.8 Most blood cells in the body develop from cells in the bone marrow.5
Long bone cross-section showing both red and yellow bone marrow.
Bone marrow stem cells
The bone marrow has two types of stem cells: mesenchymal and hematopoietic. Red bone marrow consists of a delicate, highly vascular fibrous tissue containing hematopoietic stem cells, which are blood-forming stem cells. Yellow bone marrow contains mesenchymal stem cells, also known as marrow stromal cells, which produce fat, cartilage and bone.4
Stem cells are immature (primitive) cells that have the capacity to turn into a number of different types of cell. The hematopoietic stem cells in the bone marrow give rise to two main types of cells: myeloid and lymphoid lineages, which include cells such as monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes or platelets, as well as T cells, B cells, and natural killer cells.
There are different types of hematopoietic stem cells which vary in terms of regenerative capacity and potency; some are multipotent, oligopotent or unipotent as determined by how many types of cell they can create. Pluripotent hematopoietic stem cells differ from other blood cells due to the following properties:
- Renewal: can reproduce another cell identical to itself
- Differentiation: can generate one or more subsets of more mature cells.
The process of development of different blood cells from these pluripotent stem cells is known as hematopoiesis.11
It is these stem cells that are needed in bone marrow transplant.
Stem cells constantly divide and produce new cells. Some new cells remain as stem cells and others go through a series of maturing stages (precursor or blast cells) before forming into fully formed (mature) blood cells. Stem cells rapidly multiply to make millions of blood cells each day.10
Blood cells have a limited life span (around 100-120 days for red blood cells) and are constantly being replaced. The production of healthy stem cells is vital.12
The blood vessels act as a barrier to prevent immature blood cells from leaving the bone marrow. Only mature blood cells contain the membrane proteins required to attach to and pass through the blood vessel endothelium. Hematopoietic stem cells can cross the bone marrow barrier, however, and may be harvested from peripheral (circulating) blood.15
The blood-forming stem cells in red bone marrow can multiply and mature into three significant types of blood cells, each with their own job:
- Red blood cells (erythrocytes) - transport oxygen around the body
- White blood cells (leukocytes) - help fight infection and disease. White blood cells include lymphocytes - the cornerstone of the immune system - and myeloid cells which include granulocytes: neutrophils, monocytes, eosinophils, and basophils
- Platelets (thrombocytes) - aid with clotting after injury. Platelets are fragments of the cytoplasm of megakaryocytes, another bone marrow cell.
Once mature, these blood cells migrate from the marrow and are introduced into the bloodstream, where they perform important functions required to keep the body alive and healthy.7
Mesenchymal stem cells are found in the bone marrow cavity and differentiate into a number of stromal lineages, such as chondrocytes (cartilage generation), osteoblasts (bone formation), osteoclasts, adipocytes (adipose tissue), myocytes (muscle), macrophages, endothelial cells and fibroblasts.6
Red bone marrow
All red blood cells and platelets in humans adults are formed in the red bone marrow, which also produces around 60-70% of lymphocytes (the rest begin life in the red bone marrow and become fully formed in the lymphatic tissues, including the thymus, spleen, and lymph nodes.1
Red bone marrow also plays a role in the obliteration of old red blood cells, along with the liver and spleen.
Yellow bone marrow
Yellow bone marrow's main purpose is to act as a store for fats, helping to provide sustenance and maintain the correct environment for the bone to function. However, under particular conditions, such as severe blood loss or fever, the yellow marrow may revert to red marrow.1
Yellow marrow tends to be located in the central cavities of long bones, and is generally surrounded by a layer of red marrow with long trabeculae (beam-like structures) within a sponge-like reticular framework.6
Bone marrow timeline
Bone marrow first develops in the clavicle near the end of fetal development and becomes active about 3 weeks later. Bone marrow supersedes the liver as the major hematopoietic organ at 32-36 weeks' gestation.
Bone marrow remains red until around the age of seven as the need for new continuous blood formation is high. As the body ages, the red marrow is gradually replaced by yellow fat tissue. Adults have an average of about 2.6 kg (5.7 lbs) of bone marrow, about half of which is red.3
In adults, the highest concentration of red marrow is in the bones of the vertebrae, hips (ilium), breastbone (sternum), ribs, skull and at the metaphyseal and epiphyseal ends of the long bones of the arm (humerus) and leg (femur and tibia). All other cancellous, or spongy, bones and central cavities of the long bones are filled with yellow marrow.
What does bone marrow do for your body?
The majority of red blood cells, platelets, and most of the white blood cells are formed in the red marrow. Yellow bone marrow produce fat, cartilage and bone.
White blood cells survive anywhere from a few hours to a few days, platelets for about 10 days, and red blood cells for about 120 days. These cells must be constantly replaced by the bone marrow as each blood cell has a set life expectancy.
Certain conditions may trigger additional production of blood cells, such as when the oxygen content of body tissues is low, if there is loss of blood or anemia, or if the number of red blood cells decreases. In such cases, the kidneys produce and release erythropoietin, a hormone that stimulates the bone marrow to produce more red blood cells.
Similarly, the bone marrow produces and releases more white blood cells in response to infections, and more platelets in response to bleeding. If a person experiences serious blood loss, yellow bone marrow can be activated and transformed into red bone marrow.
Blood cell formation from differentiation of hematopoietic stem cells in red bone marrow.
Healthy bone marrow is important for the following systems and activities:
The circulatory system touches every organ and system in the body and contains a number of different cells with a variety of functions. Red blood cells transport oxygen to cells and tissues, platelets are carried in the blood to help blood clot after injury, and white blood cells are transported to sites of infection or injury.
Hemoglobin is the protein in red blood cells that gives them their color. Hemoglobin collects oxygen in the lungs, transports it in the red blood cells, and releases oxygen to tissues such as the heart, muscles, and brain. Carbon dioxide (CO2), a waste product of respiration, is also removed by hemoglobin and sent back to the lungs to be exhaled.
Iron is an important nutrient for human physiology. It combines with protein to make the hemoglobin in red blood cells and is essential in the production of red blood cells (erythropoiesis). The body stores iron in the liver, spleen, and bone marrow. Most of the iron needed each day for making hemoglobin comes from the recycling of old red blood cells.
Red blood cells
The production of red blood cells is called erythropoiesis. It takes about 7 days for a committed stem cell to mature into a fully functional red blood cell. As red blood cells age, they become less active and more fragile.
Aging red cells are removed or eaten up by a type of white blood cell (macrophages) in a process known as phagocytosis and the contents of these cells are released into the blood. The iron released in this process is carried to either the bone marrow for production of new red blood cells or to the liver or other tissues for storage.
Under normal conditions, around 1% of the body's total red blood cells are replaced every day. In a healthy person, around 200 billion red blood cells are produced each day.
White blood cells
The bone marrow produces many types of white blood cells, which are necessary for a healthy immune system. These cells both prevent and fight infections.
The main types of white blood cell or leukocytes are:
Lymphocytes are produced in bone marrow. They make natural antibodies to fight infection caused by viruses that enter the body through the nose, mouth or other mucous membrane, or through cuts and grazes. Specific cells recognize the presence of foreign invaders (antigens) that enter the body and send a signal to other cells to attack the antigens.
The number of lymphocytes increases in response to these invasions. There are two major types of lymphocyte: B- and T-lymphocytes.
Monocytes are also produced in the bone marrow. Mature monocytes have a life expectancy in the blood of only 3-8 hours, but when they move into the tissues, they mature into larger cells called macrophages. Macrophages can survive in the tissues for long periods of time where they engulf and destroy bacteria, some fungi, dead cells, and other material foreign to the body.
Granulocyte is the family or collective name given to three types of white blood cells: neutrophils, eosinophils and basophils. The development of a granulocyte may take two weeks, but this time is shortened when there is an increased threat like a bacterial infection.
The bone marrow also stores a large reserve of mature granulocytes. For every granulocyte circulating within the blood, there may be 50-100 cells waiting in the marrow to be released into the blood stream. As a result, half the granulocytes in the blood stream can be available to actively fight an infection in the body within 7 hours of recognizing that an infection exists.
Once a granulocyte has left the blood it does not normally return. A granulocyte may survive in the tissues for as long as 4-5 days depending on the conditions, but it only survives for a few hours in the circulation.
Neutrophils are the most common granulocyte. They can attack and destroy bacteria and viruses.
Eosinophils are involved in the fight against many types of parasitic infections and against the larvae of parasitic worms and other organisms. They are also involved in some allergic reactions.
Basophils are the least common of the white blood cells and respond to various allergens that cause the release of histamines, heparin and other substances.
Heparin is an anticoagulant (preventing blood from clotting), and histamines are vasodilators that cause irritation and inflammation. The result of the release of these substances is to and make them more permeable, and allowing for white blood cells and proteins to enter tissues to engage the pathogen.
Platelets are produced in bone marrow by a process known as thrombopoiesis. Platelets are critical to blood coagulation and the formation of clots to stop bleeding.
Sudden blood loss triggers platelet activity at the site of an injury or wound. Here, the platelets clump together and combine with other substances to form fibrin. Fibrin has a thread-like structure and forms an external scab or clot.
Platelet deficiency causes the body to bruise and bleed more easily. Blood may not clot well at an open wound, and there may be a greater risk for internal bleeding if the platelet count is very low.
The lymphatic system is made up of lymphatic organs such as bone marrow, the tonsils, the thymus, the spleen and lymph nodes.
All lymphocytes develop in the bone marrow from immature cells called stem cells. Lymphocytes that mature in the thymus gland (behind the breastbone) are called T-cells. Lymphocytes that mature in the bone marrow or lymphatic organs are called B-cells.14
Our immune system protects the body from disease. It kills unwanted micro-organisms such as bacteria and viruses that may invade the body.
How does our immune system fight against infection?
Small glands called lymph nodes are scattered throughout the body, and once lymphocytes are made in the marrow, they travel to the lymph nodes. The lymphocytes can then travel between each node through lymphatic channels that meet at large drainage ducts that empty into a blood vessel. Lymphocytes enter the blood through these ducts.
There are three major types of lymphocytes, which play an important part of the immune system:
There are three types lymphocytes. T-lymphocytes, B-lymphocytes and natural killer cells.
These cells originate from hematopoietic stem cells in the bone marrow in mammals. B-cells express B-cell receptors (BCRs) on the surface of the cells which allow the cell to attach to an antigen on the surface of an invading microbe or other antigenic agent. For this reason, B-cells are known as antigen-presenting cells as they alert other cells of the immune system to an invading microbe.
B-cells also secrete antibodies which attach to the surface of infection-causing microbes. These antibodies are Y-shaped, and each one is akin to a specialized "lock" into which a matching antigen "key" fits. As such, each Y-shaped antibody reacts to a different microbe, triggering a larger immune system response with the aim of fighting infection.
In some circumstances, B-cells erroneously identify the normal cells of the human body as being antigens that require an immune system response. This is the mechanism that lies behind the development of autoimmune diseases such as multiple sclerosis, scleroderma and type 1 diabetes.
These cells are so-called because they mature in the thymus, a small organ in the upper chest, just behind the sternum (some T-cells mature in the tonsils). There are many different types of T-cells, and they perform a range of functions as part of adaptive cell-mediated immunity. T-cells help B-cells make antibodies against invading bacteria, viruses, or other microbes.
Unlike B-cells, some T-cells engulf and destroy pathogens directly, after binding to the antigen on the surface of the microbe.
Natural killer T-cells, not to be confused with natural killer cells of the innate immune system, bridge the adaptive and innate immune systems. NKT cells recognize antigens presented in a different way to many other antigens, and can perform the functions of T-helper cells and cytotoxic T-cells. They can also recognize and eliminate some tumor cells.
Natural killer (NK) cells
These are a type of lymphocyte that directly attacks cells which have been infected by a virus.
What are bone marrow tests?
Examination of the bone marrow is helpful in diagnosing certain diseases, especially those related to blood and blood-forming organs. Testing provides information on iron stores and blood production.1
Bone marrow aspiration uses a hollow needle to remove a small sample (about 1 ml) of bone marrow for examination under a microscope. The needle is usually inserted into the hip or sternum in adults and into the upper part of the tibia (the larger bone of the lower leg) in children and suction is used to extract the sample.
Bone marrow aspiration is typically performed when indicated by previous blood tests and is particularly useful in providing information on various stages of immature blood cells.
Disorders in which bone marrow examination is of special diagnostic value include:1
- Multiple myeloma
- Gaucher disease
- Unusual cases of anemia
- Other hematological diseases.
On the next page we take a close look at bone marrow transplants and how bone marrow is harvested. On the final page we discuss bone marrow donation and what happens when donating bone marrow.