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The marrow, located in the medullary cavity of bone, is the sole site of effective hematopoiesis in humans. The marrow produces approximately six billion cells per kilogram of body weight per day. Hematopoietically active (red) marrow regresses after birth until late adolescence, after which it is focused in the lower skull, vertebrae, shoulder and pelvic girdles, ribs, and sternum. Fat cells replace hematopoietic cells in the bones of the hands, feet, legs, and arms (yellow marrow). Fat occupies approximately 50 percent of the space of red marrow in the adult. Further fatty metamorphosis continues slowly with aging. In very old individuals, a gelatinous transformation of fat to a mucoid material may occur (white marrow). Yellow marrow can revert to hematopoietically active marrow if prolonged demand is present, as in chronic hemolytic anemia. Hematopoiesis can be expanded by increasing the volume of red marrow (expanding proliferating populations) and decreasing the development (transit) time from progenitor to mature cell.

The marrow stroma consists principally of a network of sinuses that originate at the endosteum from cortical capillaries and terminate in collecting vessels that enter the systemic venous circulation. The trilaminar sinus wall is composed of endothelial cells; an underdeveloped, thin basement membrane; and adventitial reticular cells that are fibroblasts capable of transforming into adipocytes. The endothelium and reticular cells are sources of hematopoietic cytokines. Hematopoiesis occurs in the intersinus spaces and is controlled by a complex array of stimulatory and inhibitory cytokines, cell–cell contacts, and the effects of extracellular matrix components on proximate cells. In this unique environment, lymphohematopoietic stem cells differentiate into all the blood cell lineages. Mature cells are produced and released to maintain steady-state blood cell levels. The system also can respond to meet increased demands for additional cells as a result of blood loss, hemolysis, inflammation, immune cytopenias, and other causes. Stem cells can leave and reenter marrow as part of their normal circulation. Their extramedullary circulation can be increased by exogenous cytokines and chemokines.

The evolutionary factors that led to confinement of hematopoiesis to the medullary cavity of bone are not fully understood. Two relationships that may underlie this requirement for proximity are the biochemical and receptor contributions of osteoblasts to hematopoiesis and the homing of hematopoietic stem cells to endosteum.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: IIICS, type III connecting segment; AGM, aorta-gonad-mesonephros; ALCAM, activated leukocyte adhesion molecule; bFGF, basic fibroblast growth factor; BFU-E, burst-forming unit–erythroid; BMP, bone morphogenetic protein; CAR, CXCL 12-abundant reticular cells; CD, cluster of differentiation; CFU-E, colony forming unit–erythroid; CFU-S, colony forming unit–spleen; CLA, cutaneous lymphocyte antigen; EC, endothelial cell; ECM, extracellular matrix protein; ELAM, endothelial leukocyte adhesion molecule; FN, fibronectin; GAG, glycosaminoglycan; G-CSF, granulocyte colony-stimulating factor; G-CSF-R, granulocyte colony-stimulating factor receptor; GlyCAM, glycosylation-dependent cell adhesion molecule; GM-CSF, granulocyte-macrophage colony-stimulating factor; HCA, hematopoietic cell antigen; HCAM, homing cell adhesion molecule; HGF, hepatocyte growth factor; HLA, human leukocyte antigen; HPP-CFC, ...

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