Bone Marrow - Facts, Functions and Transplants
The Importance of Bones
Bones are made of living tissue and have important functions. They store and release minerals, protect vital organs and enable us to move by providing an attachment site for muscles. Many of our bones contain cavities filled with a gelatinous material called marrow, which has additional jobs. Red bone marrow makes vital cells for our body. Yellow marrow is less active but is still useful.
Stem cells are an important component of red marrow. They produce some of the specialized cells that our body requires. Hematopoietic stem cells produce our red blood cells, white blood cells and platelets. Mesenchymal stem cells produce bone, cartilage and fat cells (adipocytes). Bone marrow transplants are used to replace stem cells that are damaged or lost.
Red and Yellow Bone Marrow
Red marrow gets its color from the numerous blood vessels that it contains. Yellow marrow contains a large amount of fat as well as blood vessels, which lightens its color. During early childhood, all of the bone marrow in the body is red. At around seven years of age, yellow marrow begins to replace some of the red kind. By the time we reach adulthood we have approximately equal amounts of each marrow color.
In an adult, red marrow is found in the skull, scapula, vertebrae, sternum, ribs, pelvis and the ends of the long bones in the arms and legs. Yellow marrow is found in the central cavity of the long bones, which is also known as the medullary cavity. In an emergency, such as after the loss of a large amount of blood, yellow marrow may be converted into the red kind.
Stem Cells and Their Uses
What are Stem Cells?
Most cells in our body are specialized for a specific function and are unable to divide, which means that they can't produce new cells. Stem cells are different from our other cells. They are unspecialized and are able to divide throughout their lives. Their job is to produce our other cells in a process called differentiation.
A stem cell divides to make two new cells. These are sometimes new stem cells that are identical to the parent cell. At the start of differentiation, however, a stem cell produces one new stem cell and a second cell which is slightly more specialized than the parent cell. This slightly specialized cell is called a progenitor cell. The progenitor cell then divides to make even more specialized cells. These cells may in turn divide to produce cells with further specializations. The process continues until the target cells are made.
Stem Cells in the Body
Bone marrow stem cells are said to be "multipotent" because one stem cell can produce several types of target cells. The specific target cells for hematopoietic stem cells are red blood cells, white blood cells and platelets. (Platelets are actually fragments of larger cells.) The target cells for mesenchymal stem cells are bone cells, cartilage cells and fat cells.
Stem cells have been found in other parts of the body in addition to bone marrow. They are generally present at low levels in these areas, however, and are often quiescent. Researchers hope that by triggering these stem cells to divide they will be able to repair or replace damaged tissues in our body. The researchers are investigating the chemical signals and environmental conditions that "tell" a stem cell to activate certain genes and make a particular target cell.
In the future, stem cells may be activated and cultured in the lab and then transplanted into the appropriate part of the body. At the moment, as the illustration above shows, only bone marrow transplants are known to be helpful.
Blood Cell Formation
Hematopoietic Stem Cells
Hematopoietic stem cells, or HSCs, make new blood cells. These cells include red blood cells, which carry oxygen from our lungs to our cells, the various types of white blood cells, which fight infection, and platelets, which help blood to clot when we're wounded.
Red blood cells live for about 120 days, many white blood cells live for only hours (although some can live for years) and platelets survive for around 8 to 10 days. These cells need to be continually replaced.
Red blood cells are also known as erythrocytes and are the most abundant cell type in blood. The bone marrow makes millions of erythrocytes every day to replace those that have died and to provide extra cells when a person's oxygen requirement increases.
There are five main types of white blood cells, or leukocytes: lymphocytes, neutrophils, eosinophils, basophils and monocytes. All of our blood cells, including all the white blood cells, are made in our bone marrow. B lymphocytes (or B cells) mature in the bone where they're made, while T lymphocytes (or T cells) migrate to the thymus gland to mature. The thymus gland is located in the upper part of the chest.
In order to make platelets, or thrombocytes, hematopoietic stem cells produce giant cells called megakaryocytes. These cells are ten to fifteen times larger than red blood cells and have a very large nucleus. They fragment as they make platelets.
Mesenchymal Stem Cells
Bone marrow also contains mesenchymal stem cells, or MSCs, which are sometimes known as stromal stem cells. These produce new bone-building cells (osteoblasts), new cartilage cells (chondrocytes) and new adipocytes. There are far fewer MSCs in bone than HSCs. Mesenchymal stem cells are still important, however. Cells resembling mesenchymal stem cells are found in other parts of the body, but it's unclear how similar their activity is to the ones in bone.
Bone Marrow Transplants
A bone marrow transplant may be needed when the patient's own marrow becomes damaged or fails to function properly. When donated stem cells enter the bone, they produce healthy and functioning stem cells as well as target cells.
One problem with any type of transplant is that the recipient's body may attack and destroy the donated cells. This is why doctors look for donor cells that have membrane similarities to the patient's cells before they perform a transplant. The membrane is the outer layer of a cell. The body doesn't normally attack cells which it recognizes as "self". It distinguishes self from non-self by detecting the presence of membrane proteins.
Before a marrow transplant takes place, doctors or medical technicians test for the presence of specific proteins on the cell membranes of the donor cells. These proteins are called human leukocyte-assisted antigens, or HLA antigens. The more similar these proteins in a donor and recipient, the greater the probability that a transplant will be successful.
Disorders That May Be Treated with a Bone Marrow Transplant
There are many disorders whose treatment may involve a bone marrow transplant. These include disorders in which the bone marrow fails to do its job properly, diseases in which medical treatments destroy bone marrow cells and certain inherited blood disorders in which faulty red blood cells or faulty hemoglobin are made. Three examples of conditions that may be helped by a marrow transplant are described below.
Autoimmune Aplastic Anemia
In aplastic anemia, the stem cells in the bone marrow are injured and the bone doesn't make enough new blood cells. The disease may be inherited or acquired during life.
Acquired aplastic anemia is the more common disorder. It may arise due to exposure to toxins, certain medications or certain viruses. Radiation or chemotherapy treatment for cancer may also damage or destroy bone marrow cells. In addition, it's thought that in some people aplastic anemia may be an autoimmune disease. In this type of disease the immune system mistakenly attacks the body's own cells. Sometimes the cause of aplastic anemia is unknown.
Aplastic anemia may be temporary and disappear with no treatment. It may be a mild condition, but it can sometimes be serious. The disorder is often helped by blood transfusions. Medicines that stimulate marrow to make blood cells or that suppress an overactive immune system may also be helpful. A marrow transplant may be recommended as a treatment for severe aplastic anemia.
Cancer Treatment and Bone Marrow Destruction
Some types of cancer are treated with powerful chemicals (chemotherapy) or high-dose radiation. These treatments destroy cells that divide rapidly, such as cancer cells. Bone marrow cells also divide rapidly, however, and may be destroyed by the cancer treatment. Doctors use bone marrow transplants to restore stem cells after the cancer has been cured. There are three types of transplants.
- In an autologous transplant, a patient receives their own stem cells which were removed before the cancer treatment began.
- In a syngeneic transplant, a person receives stem cells from their identical twin.
- In an allogeneic transplant, a person receives stem cells from a relative or from an unrelated person whose cells are similar enough that they are not likely to be rejected. (Unless the donated cells are genetically identically to the recipient's cells there is no guarantee that rejection won't occur, however.)
Some types of cancer originate in the bone marrow. The treatment for these cancers may involve destruction of cancer cells followed by a stem cell transplant.
Thalassemia is an inherited condition in which an abnormal form of hemoglobin is made. Hemoglobin is the protein in red blood cells that attaches to oxygen and carries it around the body. Red blood cells with abnormal hemoglobin don't work as effectively as healthy red blood cells and tend to die earlier. A person with thalassemia may have no symptoms, mild symptoms or serious symptoms, depending on the nature of the genetic problem.
Thalassemia may be treated by regular transfusions of normal blood or by folic acid supplements to encourage the formation of new red blood cells. One problem with receiving frequent blood transfusions is that an excessively high level of iron may build up in the patient's body, since blood contains iron. The patient may need therapy to remove the iron.
Sometimes a bone marrow transplant is used as a treatment for thalassemia, especially in children with a severe form of the disease. The defective bone marrow is generally destroyed by radiation or drugs before the transplant is performed. Bone marrow transplants have helped children with thalassemia to live normal lives.
Peripheral Blood Stem Cell Donation
How are a Bone Marrow Donation and Transplant Performed?
There are two ways to obtain bone marrow cells from a donor. One method is similar to donating blood and is called peripheral blood stem cell donation, or PBSC donation. The other process involves surgery.
In peripheral blood stem cell donation, the donor is first given injections of a chemical called filgastrim for four or five days to increase the number of bone marrow stem cells. Some of these cells enter the blood. Blood is then taken from the donor and the stem cells are removed by a device called an apheresis machine. After this removal, the blood is returned to the donor. The donation process takes between four and six hours.
The donated cells are injected into the recipient and migrate to his or her bone marrow. This process is often referred to as a bone marrow donation, even though this term isn't accurate, since stem cells are being donated instead of bone marrow.
Marrow may also be removed from a donor's pelvis while he or she is under a general anesthetic. Since the donor is unconscious the procedure is painless, but there may be soreness afterwards. The procedure is sometimes performed after regional anesthesia. In this state the donor is conscious but has no feeling below the waist. Stem cells from the donated bone marrow are injected into the recipient's bloodstream and travel to their bone marrow.
Donating Bone Marrow from the Pelvis
Bone marrow transplants may be very successful and save lives. Sometimes problems develop, however. The body may destroy the donated cells or medical complications may arise from the transplant.
Researchers are investigating ways to improve both the effectiveness and the safety of bone marrow transplants. Their research may help to improve other types of transplants and may reveal more about the behavior of stem cells. Stem cell research is very exciting and may have wonderful benefits in the future.
References and Further Reading
© 2013 Linda Crampton