Bone marrow – Structure, Composition and Functions

Bone marrow is soft, spongy, gelatinous tissue that fills the centers of bones known as medullary cavities.

Bone marrow is highly vascular meaning that it is enriched with blood vessels and capillaries. Each day bone marrow produces hundreds of billions of new blood cells.

Bone marrow takes over from the liver as the major hematopoietic organ at 32 to 36 weeks’ gestation.

Types of Bone Marrow

Red Bone Marrow

It is also known as myeloid tissue. Its main function is to produce blood cells. In addition, it also helps to remove old cells from blood circulation (spleen and liver also remove old and damaged blood cells from the blood).

From birth to early adolescence, the majority of our bone marrow is red marrow. With increasing age, red marrow is replaced by yellow marrow.

In adults, red marrow is confined mostly to bones of the skull, pelvis, spine, ribs, sternum, vertebrae, shoulder blades, and epiphyseal and metaphyseal ends of the long bones of the arms (humerus) and legs (femur and tibia).

All other cancellous or spongy bones and central cavities of the long bones are filled with yellow marrow.

Red bone marrow consists of a delicate, highly vascular fibrous tissue which contains hematopoietic stem cells. These are blood-forming stem cells and are of two types: myeloid stem cells and lymphoid stem cells.

These cells develop into red blood cells, white blood cells, and platelets.

Yellow Bone Marrow

It is also known as fatty bone marrow as it consists mainly of fat cells.

 It is found in spongy bones and in the shaft of long bones. Its main function is to store fat. It also helps to provide sustenance and maintain the correct environment for the bone to function.

It is composed of hematopoietic tissue that has become inactive. In conditions such as massive blood loss, when blood cells become extremely low, yellow marrow can be converted to red marrow in order to produce more blood cells.

Bone Marrow Stem Cells

The bone marrow contains two types of stem cells, mesenchymal and hematopoietic.

Mesenchymal Stem Cells

These are also known as marrow stromal cells. They are found in yellow marrow. These produce non-blood cell components of marrow including

• Fat cells (adipose tissue)
• Chondrocytes (cartilage)
• Fibroblasts (fibrous connective tissue)
• Stromal cells (that support blood formation)
• Osteoblasts (for bone synthesis)
• Osteoclasts (for bone resorption)

Hematopoietic Stem Cells

They are found in the red marrow and are responsible for the production of blood cells. They are immature cells that can turn into a number of different types of blood cells.

The different types of hematopoietic stem cells have different regenerative capacity and potency. Based on the types of cells they can create, they can be classified as pluripotent, multipotent, oligopotent or unipotent. They rapidly multiply and undergo maturation through different stages to produce mature blood cells. Millions of blood cells are produced each day.

The process of development of different blood cells from the pluripotent stem cells is known as hematopoiesis.

Hematopoietic stem cells are of two types: myeloid stem cells and lymphoid stem cells.

Myeloid Stem Cells

They develop into red blood cells, platelets, mast cells, or myeloblast cells. Myeloblast cells develop into granulocyte and monocyte white blood cells.

• Red blood cells or erythrocytes: These cells transport oxygen throughout the body.
• Megakaryocytes and platelets: Megakaryocytes are large cells that break into fragments to give rise to platelets or thrombocytes, The main function of platelets is to help in blood clotting after an injury.
• Myeloblast: They give rise to granulocytes or white blood cells (neutrophils, eosinophils, and basophils). These cells protect the body against various infections (bacterial, viral, protozoan) and become active during allergic reactions.
• Monocytes: These are also a type of white blood cells. They migrate from blood to body tissues and develop into macrophages and dendritic cells. Their main function of macrophages is to remove foreign substances, pathogens, dead or damaged cells from the body by phagocytosis.
• Dendritic cells: They present antigenic information to lymphocytes, thereby helping in the development of antigen immunity.
• Mast Cells: These cells are found throughout body tissues. They are mainly found in the skin and mucosal lining of the digestive system. They also play a role in mediating the immune responses by releasing chemicals, such as histamine which is stored in their granules.

Lymphoid Stem Cells

They develop into lymphoblast cells which produce lymphocytes. Lymphocytes include natural killer cells, B lymphocytes, and T lymphocytes.

• Natural Killer Cells – These cytotoxic cells contain enzymes that cause apoptosis in infected and diseased cells. They form part of body’s innate immune response.
• B Cell Lymphocytes – These cells have a role in adaptive immunity. They recognize molecular signals from pathogens and produce antibodies against specific antigens.
• T Cell Lymphocytes – These cells are active in cell-mediated immunity. They help to identify and destroy damaged, cancerous, and infected cells.

There is biologic compartmentalization in the bone marrow. This means that certain cell types tend to aggregate in specific areas. For eg, RBCs, macrophages, as well as their precursor forms have a tendency to be present around blood vessels, while WBCs and their precursors gather at the borders of the bone marrow.

Once mature, these blood cells move from the bone marrow into the bloodstream, where they perform their respective functions.

Within the circulation, blood cells have a limited lifespan. For e.g., RBCs have a lifespan of 100-120 days. WBCs survive from a few hours to few days while platelets have a lifespan of about 8-9 days. The bone marrow constantly replaces old and damaged cells by producing new blood cells.

Functions of Bone Marrow

Hematopoiesis

Bone marrow is the site for hematopoiesis. All the blood cells are produced in the bone marrow. However, some white blood cells after being produced in the bone marrow migrate to other lymphoid organs such as the spleen, lymph nodes, and thymus gland for maturation.

Stem Cells

Bone marrow acts as a reservoir of stem cells – both hematopoietic and mesenchymal.

Hematopoietic stem cells are harvested from bone marrow or peripheral blood for purpose of bone marrow/ stem cell transplantation.

Bone Marrow Barrier

The blood vessels of the bone marrow form a barrier, which does not allow immature blood cells to enter into the circulation as they do not possess the membrane proteins which are necessary to attach to and pass through the blood vessel endothelium. However, the hematopoietic stem cells are able to cross the bone marrow barrier and hence can be harvested from blood.

In a few diseased conditions, the immature cells may get released into the circulation. These include conditions like hemolytic anemia in which bone marrow produces an increased number of cells to compensate for the hemolysis or in leukemias when a large number of immature cells are being produced and there is a failure of maturation.

Lymphatic Role

The red bone marrow is an important element of the lymphatic system since it produces lymphocytes. Both the bone marrow and thymus constitute primary lymphoid tissue as they are involved in the production and early selection of lymphocytes. In addition, bone marrow also performs a valve-like function and does not allow the lymphatic fluid to flow back into the lymphatic system.

Clinical Significance of Bone Marrow

Diseases

Bone marrow can be affected by a variety of disorders. These include infections (including tubercular), aplastic anemia, metastatic malignancies, etc. leading to a decrease in the production of different blood cells. In addition, the hematologic progenitor cells in the bone marrow can turn malignant, resulting in various types of blood cancer (leukemias, multiple myeloma, etc).

Exposure to radiation or chemotherapeutic drugs can kill most of the rapidly dividing cells of the bone marrow and will, therefore, result in the reduction in all the formed elements of blood and a depressed immune system.

Bone Marrow Aspiration and Biopsy

It is a medical procedure done to diagnose diseases involving the bone marrow. In bone marrow aspiration, a hollow needle is inserted into the bone (posterior superior iliac spine or sternum) and a small sample of red bone marrow is aspirated under local anesthesia. This material is then spread on a glass slide, stained appropriately and examined under a microscope.

Bone marrow biopsy is usually carried out from the posterior superior iliac spine by using a different needle. The tissue obtained is decalcified, processed and then examined microscopically.

Bone Marrow / Stem Cell Transplant

In this procedure, hematopoietic stem cells are removed from a person and infused into another person (allogenic) or into the same person at a later time (autologous). This procedure can be carried out for a number of hematological or non-hematological conditions. It is a high-risk procedure and is reserved for patients  with life-threatening diseases

• Leukemias
• Lymphomas
• Multiple myeloma
• Neuroblastoma
• Ewing sarcoma
• Myelodysplastic syndromes
• Gliomas other solid tumors
• Thalassemia
• Sickle cell anemia
• Aplastic anemia
• Fanconi anemia
• Malignant infantile osteopetrosis
• Mucopolysaccharidosis
• Immune deficiency syndromes
• Autoimmune diseases

Therapeutic Role of Stem cells

Since stem cells derived from the bone marrow are pluripotent, they can give rise to various cell lineages and tissues. This can be helpful in regenerative medicine. Although still in experimental stages, it can revolutionize the treatment of various chronic and degenerative diseases.