I
INTRODUCTION

Bone Marrow, soft, pulpy tissue that fills the cavities of bones, occurring in two forms, red and yellow. One of the largest tissues in the body, bone marrow accounts for 2 to 5 percent of an adult’s weight. Red marrow, present in all bones at birth, serves as the blood manufacturing center. As an infant matures, most of the red marrow in the shaft of long bones, such as the arm and leg bones, is gradually replaced by yellow marrow. Yellow marrow is composed primarily of specialized fat cells.

II
STRUCTURE

Cross Section of a Bone

Bone marrow, the soft, pulpy tissue that fills bone cavities, contains a network of blood vessels and fibers surrounded by fat and blood-producing cells. In children, the cells that give rise to blood cells can be found throughout the marrow. In adults, these cells are found mostly in the red marrow of the bones of the chest, hips, back, skull, and of the upper arms and legs. The marrow in the long shafts of bones gradually loses its ability to manufacture blood. This marrow, which is dominated by fat cells and takes on a yellowish color, is called yellow marrow. This cross section of a long bone shows yellow bone marrow in the shaft of a long bone.

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Red marrow consists primarily of a loose, soft network of blood vessels and protein fibers interspersed with developing blood cells. The blood vessels are termed the vascular component, and the protein fibers and developing blood cells collectively are referred to as the stroma, or the extravascular component. The protein fibers crisscross the marrow, forming a meshwork that supports the developing blood cells clustered in the spaces between the fibers.

Red marrow contains a rich blood supply. Arteries transport blood containing oxygen and nutrients into the marrow, and veins remove blood containing carbon dioxide and other wastes. The arteries and veins are connected by capillaries, blood vessels that branch throughout the marrow. In various places, the capillaries balloon out, forming numerous thin, blood-filled cavities. These cavities are called sinusoids, and they assist in blood-cell production.

Yellow marrow is so named because it is composed of yellow fat cells interspersed in a rich mesh of connective tissue that also supports many blood vessels. While not usually actively involved in blood formation, in an emergency yellow marrow is replaced by blood-forming red marrow when the body needs more blood.

MARROW FUNCTION

Constituents of Blood

In an average healthy person, approximately 45 percent of the blood volume is cells, produced in the red bone marrow. Within the bone marrow, all blood cells originate from one type of cell called a hematopoietic stem cell. These stem cells divide to become progenitor blood cells, which undergo further specializations to become red blood cells, white blood cells, or platelets. Blood also contains a clear, yellowish fluid called plasma. The test tube on the right has been centrifuged to separate plasma and packed cells by density.

Martin M. Rotker/Science Source/Photo Researchers, Inc.

Red marrow produces all of the body’s blood cells—red blood cells, white blood cells, and platelets. Red blood cells in the circulatory system transport oxygen to body tissues and carbon dioxide away from tissues. White blood cells are critical for fighting bacteria and other foreign invaders of the body (see Immune System). Platelets are essential for the formation of blood clots to heal wounds.

Within red bone marrow, all blood cells originate from a single type of cell, called a hematopoietic stem cell. Stimulated by hormones and growth factors, these stem cells divide to produce immature, or progenitor blood cells. Most of these progenitor cells remain in the stroma and rapidly undergo a series of cell divisions, producing either red blood cells or white blood cells. At any one time, the stroma consists largely of progenitor cells in various stages of development. At the appropriate developmental stage, the fresh, new cells squeeze through the walls of the capillaries. From there, the cells leave the bone and enter the body’s circulatory system. Some progenitor cells migrate to the sinusoids, where they produce platelets, which also travel to the circulatory system via the capillaries.

Although stem cells are relatively rare—about 1 in every 10,000 marrow cells is a stem cell—they typically produce the forerunners of an estimated 2 million red cells per second and 2 billion platelets per day. However, if significant amounts of blood are lost or other conditions reduce the supply of oxygen to tissues, the kidneys secrete the hormone erythropoietin. This hormone stimulates stem cells to produce more red blood cells. To fight off infection, hormones collectively termed colony stimulating growth factors are released by the immune system. These hormones stimulate the stem cells to produce more infection-fighting white blood cells. And in severe cases, the body converts yellow marrow into red marrow to help produce needed blood cells.

BONE MARROW DISEASES

Hairy Cell Leukemia

About 30,000 new cases of cancer of the bone marrow, or leukemia, are diagnosed each year in the United States. There are four types of leukemia, classified by the type of blood cell affected and whether the cells are mature or immature. Pathologists can distinguish various types of leukemia by the appearance of the cancerous cells underneath a microscope. A magnification of a cell affected by hairy cell leukemia, shown here, reveals the characteristic minute, hairlike projections on the cell surface.

Aaron Polliack/Science Photo Library/Photo Researchers, Inc.

Diseases of the bone marrow can be life threatening because they disrupt blood cell production, which is essential for survival. Inadequate production of blood cells results in aplastic anemia. The causes of this relatively rare disease are often unknown, although some cases result from exposure to toxic chemicals, such as lead, benzene, or arsenic. Radiation from nuclear explosions or X rays can also damage the marrow because the radioactive elements involved have a strong affinity for bone marrow.

Leukemias are cancers that affect bone marrow (as well as other tissues). A cell can become cancerous at any state during the series of divisions that produce red or white blood cells. If a progenitor cell becomes cancerous at the beginning of a series of cell divisions, the leukemia is termed acute. Chronic leukemia results when cells in later stages of division become cancerous.

Bone Marrow Transplants

Radiation Treatment

Radiation therapy, sometimes used to shrink collections of cancerous cells, can severely damage a patient’s bone marrow. To compensate for bone marrow lost in radiation treatments, patients are increasingly undergoing a kind of bone marrow transplant called stem cell transplant. In this procedure, prior to radiation treatment a patient’s own stem cells are extracted and the cancerous cells removed. After the radiation therapy is complete, the healthy stem cells are returned to the bloodstream.

Martin Dohrn/Science Source/Photo Researchers, Inc.

Bone marrow transplants treat a variety of blood and bone marrow diseases (see Medical Transplantation). In a conventional transplant, a donor and recipient are matched as closely as possible for blood type. The red marrow from the donor is suctioned from the pelvic bone with a long needle attached to a syringe. The marrow sample is treated to remove the donor’s white blood cells, which otherwise would attack the recipient’s tissues. The treated marrow is then given to the recipient through an intravenous infusion, which introduces immature, but healthy, cells into the bloodstream. These cells migrate to the marrow, where they mature and eventually divide, populating the circulatory system with healthy cells. The transplanted stem cells serve as a continual source of healthy cells. While bone marrow transplants are helpful, they cannot always cure a blood or bone marrow disease because the match between donor and recipient is seldom perfect. The immune system of the recipient may attack some of the donor’s cells, which interferes with the benefits of the transplant.

Increasingly, only the stem cells from a bone marrow are used in a bone marrow transplant. Called a stem cell transplant, this procedure is often used for cancer patients who will be undergoing extensive radiation and chemotherapy treatments that will likely irreparably damage the bone marrow. Prior to undergoing radiation or chemotherapy, some of the patient’s own marrow is removed and screened to eliminate cancer cells in a technique called a stem cell wash. The population of healthy stem cells is kept alive in the laboratory. After the chemotherapy and radiation treatments, the patient’s stem cells are returned to the bloodstream. They travel to the marrow and begin the process of blood cell production. The advantage of this type of stem cell transplant—in which the patient is both donor and recipient—is that the immune system will not be activated to destroy the transplanted cells. The disadvantage is that it takes longer for functioning cells to get into the blood stream, since only stem cells, and not cells in all stages of development, are transferred.

A newer stem cell transplant technique involves injecting a patient with high doses of the growth factors that stimulate white blood cell production. This causes stem cells to be released into the blood stream. The blood is then drawn and the stem cells are harvested. This technique has the advantage of being less invasive than retrieving stem cells from bone marrow.

Other types of stem cell transplants, which require both a donor and a recipient, are used to correct genetic disorders such as sickle-cell anemia, in which red blood cells are distorted and unable to transport oxygen properly. Sometimes the source of stem cells for these transplants is blood from the umbilical cord or placenta of a newborn infant. New techniques that match the blood cell producing genes of donors and recipients rather than the blood types may offer more success in these transplants.

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