Bone marrow: Function, diseases, transplants, and donation
By daniellenierenberg
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.
Many people with blood cancers, such as leukemia and lymphoma, sickle cell anemia, and other life threatening conditions rely on bone marrow or cord blood transplants to survive.
People need healthy bone marrow and blood cells to live. When a condition or 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 people, it may be the only option.
This article looks at everything there is to know about bone marrow.
Bone marrow is soft, gelatinous tissue that fills the medullary cavities, or the centers of bones. The two types of bone marrow are red bone marrow, known as myeloid tissue, and yellow bone marrow, known as fatty tissue.
Both types of bone marrow are enriched with blood vessels and capillaries.
Bone marrow makes more than 220 billion new blood cells every day. Most blood cells in the body develop from cells in the bone marrow.
Bone marrow contains two types of stem cells: mesenchymal and hematopoietic.
Red bone marrow consists of a delicate, highly vascular fibrous tissue containing hematopoietic stem cells. These are blood-forming stem cells.
Yellow bone marrow contains mesenchymal stem cells, or marrow stromal cells. These produce fat, cartilage, and bone.
Stem cells are immature cells that can turn into a number of different types of cells.
Hematopoietic stem cells in the bone marrow give rise to two main types of cells: myeloid and lymphoid lineages. These include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, dendritic cells, and megakaryocytes, or platelets, as well as T cells, B cells, and natural killer (NK) cells.
The different types of hematopoietic stem cells vary in their regenerative capacity and potency. They can be multipotent, oligopotent, or unipotent, depending on how many types of cells they can create.
Pluripotent hematopoietic stem cells have renewal and differentiation properties. They can reproduce another cell identical to themselves, and they can generate one or more subsets of more mature cells.
The process of developing different blood cells from these pluripotent stem cells is known as hematopoiesis. It is these stem cells that are needed in bone marrow transplants.
Stem cells constantly divide and produce new cells. Some new cells remain as stem cells, while others go through a series of maturing stages, as precursor or blast cells, before becoming formed, or mature, blood cells. Stem cells rapidly multiply to make millions of blood cells each day.
Blood cells have a limited life span. This is around 120 days for red blood cells. The body is constantly replacing them. The production of healthy stem cells is vital.
The blood vessels act as a barrier to prevent immature blood cells from leaving 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. Healthcare professionals may harvest these from peripheral, or circulating, blood.
The blood-forming stem cells in red bone marrow can multiply and mature into three significant types of blood cells, each with its own job:
Once mature, these blood cells move from bone marrow into the bloodstream, where they perform important functions that keep the body alive and healthy.
Mesenchymal stem cells are present in the bone marrow cavity. They can differentiate into a number of stromal lineages, such as:
Red bone marrow produces all red blood cells and platelets and around 6070% of lymphocytes in human adults. Other lymphocytes begin life in red bone marrow and become fully formed in the lymphatic tissues, including the thymus, spleen, and lymph nodes.
Together with the liver and spleen, red bone marrow also plays a role in getting rid of old red blood cells.
Yellow bone marrow mainly acts as a store for fats. It helps provide sustenance and maintain the correct environment for the bone to function. However, under particular conditions such as with severe blood loss or during a fever yellow bone marrow may revert to red bone marrow.
Yellow bone marrow tends to be located in the central cavities of long bones and is generally surrounded by a layer of red bone marrow with long trabeculae (beam-like structures) within a sponge-like reticular framework.
Before birth but toward the end of fetal development, bone marrow first develops in the clavicle. It becomes active about 3 weeks later. Bone marrow takes over from the liver as the major hematopoietic organ at 3236 weeks gestation.
Bone marrow remains red until around the age of 7 years, as the need for new continuous blood formation is high. As the body ages, it gradually replaces the red bone marrow with yellow fat tissue. Adults have an average of about 2.6 kilograms (kg) (5.7 pounds) of bone marrow, about half of which is red.
In adults, the highest concentration of red bone marrow is in the bones of the vertebrae, hips (ilium), breastbone (sternum), ribs, and skull, as well as 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 bone marrow.
Most red blood cells, platelets, and most white blood cells form in the red bone marrow. Yellow bone marrow produces fat, cartilage, and bone.
White blood cells survive from a few hours to a few days, platelets for about 10 days, and red blood cells for about 120 days. Bone marrow needs to replace these cells constantly, as each blood cell has a set life expectancy.
Certain conditions may trigger additional production of blood cells. This may happen 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. If these things happen, the kidneys produce and release erythropoietin, which is a hormone that stimulates bone marrow to produce more red blood cells.
Bone marrow also 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 activate and transform into red bone marrow.
Healthy bone marrow is important for a range of systems and activities.
The circulatory system touches every organ and system in the body. It involves a number of different cells with a variety of functions. Red blood cells transport oxygen to cells and tissues, platelets travel in the blood to help clotting after injury, and white blood cells travel to sites of infection or injury.
Hemoglobin is the protein in red blood cells that gives them their color. It collects oxygen in the lungs, transports it in the red blood cells, and releases oxygen to tissues such as the heart, muscles, and brain. Hemoglobin also removes carbon dioxide (CO2), which is a waste product of respiration, and sends it back to the lungs for exhalation.
Iron is an important nutrient for human physiology. It combines with protein to make the hemoglobin in red blood cells and is essential for producing red blood cells (erythropoiesis). The body stores iron in the liver, spleen, and bone marrow. Most of the iron a person needs each day for making hemoglobin comes from the recycling of old 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.
White blood cells called macrophages remove aging red cells in a process known as phagocytosis. The contents of these cells are released into the blood. The iron released in this process travels either to bone marrow for the production of new red blood cells or to the liver or other tissues for storage.
Typically, the body replaces around 1% of its total red blood cell count every day. In a healthy person, this means that the body produces around 200 billion red blood cells each day.
Bone marrow produces many types of white blood cells. These are necessary for a healthy immune system. They prevent and fight infections.
The main types of white blood cells, or leukocytes, are as follows.
Lymphocytes are produced in bone marrow. They make natural antibodies to fight infection due to viruses that enter the body through the nose, mouth, or another mucous membrane or through cuts and grazes. Specific cells recognize the presence of invaders (antigens) that enter the body and send a signal to other cells to attack them.
The number of lymphocytes increases in response to these invasions. There are two major types of lymphocytes: B and T lymphocytes.
Monocytes are produced in bone marrow. Mature monocytes have a life expectancy in the blood of only 38 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 that is foreign to the body.
Granulocytes is the collective name given to three types of white blood cells: neutrophils, eosinophils, and basophils. The development of a granulocyte may take 2 weeks, but this time reduces when there is an increased threat, such as a bacterial infection.
Bone marrow stores a large reserve of mature granulocytes. For every granulocyte circulating in the blood, there may be 50100 cells waiting in the bone marrow to be released into the bloodstream. As a result, half the granulocytes in the bloodstream can be available to actively fight an infection in the body within 7 hours of it detecting one.
Once a granulocyte has left the blood, it does not usually return. A granulocyte may survive in the tissues for up to 45 days, depending on the conditions, but it can only survive for a few hours in circulating blood.
Neutrophils are the most common type of 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. They respond to various allergens that cause the release of histamines, heparin, and other substances.
Heparin is an anticoagulant. It prevents blood from clotting. Histamines are vasodilators that cause irritation and inflammation. Releasing these substances makes a pathogen more permeable and allows for white blood cells and proteins to enter the tissues to engage the pathogen.
The irritation and inflammation in tissues that allergens affect are parts of the reaction associated with hay fever, some forms of asthma, hives, and, in its most serious form, anaphylactic shock.
Bone marrow produces platelets in a process known as thrombopoiesis. Platelets are necessary for blood to coagulate and for clots to form in order 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 higher risk of internal bleeding if the platelet count is very low.
The lymphatic system consists of lymphatic organs such as bone marrow, the tonsils, the thymus, the spleen, and lymph nodes.
All lymphocytes develop in bone marrow from immature cells called stem cells. Lymphocytes that mature in the thymus gland (behind the breastbone) are called T cells. Those that mature in bone marrow or the lymphatic organs are called B cells.
The immune system protects the body from disease. It kills unwanted microorganisms such as bacteria and viruses that may invade the body.
Small glands called lymph nodes are located throughout the body. Once lymphocytes are made in bone 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.
Three major types of lymphocytes play an important part in the immune system: B lymphocytes, T lymphocytes, and NK cells.
These cells originate from hematopoietic stem cells in bone marrow in mammals.
B cells express B cell receptors on their surface. These allow the cell to attach to an antigen on the surface of an invading microbe or another antigenic agent.
For this reason, B cells are known as antigen-presenting cells, as they alert other cells of the immune system to the presence of an invading microbe.
B cells also secrete antibodies that 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. Because of this, each Y-shaped antibody reacts to a different microbe, triggering a larger immune system response to fight infection.
In some circumstances, B cells erroneously identify healthy cells as being antigens that require an immune system response. This is the mechanism behind the development of autoimmune conditions such as multiple sclerosis, scleroderma, and type 1 diabetes.
These cells are so-called because they mature in the thymus, which is 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.
NK T cells, not to be confused with NK cells of the innate immune system, bridge the adaptive and innate immune systems. NK T cells recognize antigens presented in a different way from many other antigens, and they can perform the functions of T helper cells and cytotoxic T cells. They can also recognize and eliminate some tumor cells.
These are a type of lymphocyte that directly attack cells that a virus has infected.
A bone marrow transplant is useful for various reasons. For example:
Stem cells mainly occur in four places:
Stem cells for transplantation are obtainable from any of these except the fetus.
Hematopoietic stem cell transplantation (HSCT) involves the intravenous (IV) infusion of stem cells collected from bone marrow, peripheral blood, or umbilical cord blood.
This is useful for reestablishing hematopoietic function in people whose bone marrow or immune system is damaged or defective.
Worldwide, more than 50,000 first HSCT procedures, 28,000 autologous transplantation procedures, and 21,000 allogeneic transplantation procedures take place every year. This is according to a 2015 report by the Worldwide Network for Blood and Marrow Transplantation.
This number continues to increase by over 7% annually. Reductions in organ damage, infection, and severe, acute graft-versus-host disease (GVHD) seem to be contributing to improved outcomes.
In a study of 854 people who survived at least 2 years after autologous HSCT for hematologic malignancy, 68.8% were still alive 10 years after transplantation.
Bone marrow transplants are the leading treatment option for conditions that threaten bone marrows ability to function, such as leukemia.
A transplant can help rebuild the bodys capacity to produce blood cells and bring their numbers to acceptable levels. Conditions that may be treatable with a bone marrow transplant include both cancerous and noncancerous diseases.
Cancerous diseases may or may not specifically involve blood cells, but cancer treatment can destroy the bodys ability to manufacture new blood cells.
A person with cancer usually undergoes chemotherapy before transplantation. This eliminates the compromised marrow.
A healthcare professional then harvests the bone marrow of a matching donor which, in many cases, is a close family member and ready it for transplant.
Types of bone marrow transplant include:
A persons tissue type is defined as the type of HLA they have on the surface of most of the cells in their body. HLA is a protein, or marker, that the body uses to help it determine whether or not the cell belongs to the body.
To check if the tissue type is compatible, doctors assess how many proteins match on the surface of the donors and recipients blood cells. There are millions of different tissue types, but some are more common than others.
Tissue type is inherited, and types pass on from each parent. This means that a relative is more likely to have a matching tissue type.
However, if it is not possible to find a suitable bone marrow donor among family members, healthcare professionals try to find someone with a compatible tissue type on the bone marrow donor register.
Healthcare professionals perform several tests before a bone marrow transplant to identify any potential problems.
These tests include:
In addition, a person needs a complete dental exam before a bone marrow transplant to reduce the risk of infection. Other precautions to lower the risk of infection are also necessary before the transplant.
Bone marrow is obtainable for examination by bone marrow biopsy and bone marrow aspiration.
Bone marrow harvesting has become a relatively routine procedure. Healthcare professionals generally aspirate it from the posterior iliac crests while the donor is under either regional or general anesthesia.
Healthcare professionals can also take it from the sternum or from the upper tibia in children, as it still contains a substantial amount of red bone marrow.
To do so, they insert a needle into the bone, usually in the hip, and withdraw some bone marrow. They then freeze and store this bone marrow.
National Marrow Donor Program (NMDP) guidelines limit the volume of removable bone marrow to 20 milliliters (ml) per kg of donor weight. A dose of 1 x 103 and 2 x 108 marrow mononuclear cells per kg is necessary to establish engraftment in autologous and allogeneic marrow transplants, respectively.
Complications related to bone marrow harvesting are rare. When they do occur, they typically involve problems related to anesthetics, infection, and bleeding.
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