Structure and function of the bone marrow and hematopoiesis

Bone marrow, a well-organized tissue located within the bone cavities, is richly innervated and highly vascularized but devoid of lymphatics. Structurally, it consists of two major cellular elements, the stromal cells (reticular cells--fibroblasts, endothelial cells, adipocytes, and so on) and the parenchymal cells (hematopoietic cells). Functionally, it serves as the primary site for hematopoiesis and as a major reticuloendothelial organ involved in immune responses (cellular and humoral) and removal of senescent and abnormal cells and particulate material. An uncommitted pluripotential hematopoietic stem cell, itself a product of the differentiation of mesenchymal cells of the yolk sac and capable of self-replication, undergoes proliferation and differentiation in an orderly manner, generating immature committed progenitors with uni-, bi-, or trilineage specificity. These committed progenitors also multiply and differentiate in a sequential fashion, ultimately producing mature cells that are released into the circulation. Under steady state conditions, the cell death/loss is balanced by cell production by virtue of regulatory mechanisms that apparently involve (1) cell-cell interaction between marrow cells and (2) production of humoral growth and/or inhibitory factors by stromal and parenchymal cells individually or in concert. Some of these regulators of hematopoiesis have been isolated, purified, molecularly cloned, and characterized. The availability of recombinant growth factors has stimulated clinical trials of these factors as therapeutic agents.