The marrow, located in the medullary cavity of bone, is the site of hematopoiesis in humans*. The marrow produces approximately 6 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% of the space of red marrow in the adult, and fatty metamorphosis continues slowly with aging. 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 the 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 near 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; a thin basement membrane; and mesenchymal adventitial reticular cells that give rise to osteogenic-adipogenic cells. The endothelium and reticular cells are also sources of hematopoietic cytokines. Hematopoiesis occurs in the spaces between sinuses and is controlled by a complex array of stimulatory and inhibitory cytokines, cell–cell contacts, and extracellular matrix components. Lymphohematopoietic stem cells can leave and reenter marrow as part of their normal circulation. Their extramedullary circulation can be increased by exogenous cytokines and chemokines. Within the unique marrow environment, the hematopoietic stem cells differentiate into all the blood cell lineages. Mature cells are produced and released to maintain steady-state blood cell levels. The system can respond to meet increased demands for additional cells as a result of blood loss, hemolysis, inflammation, immune cytopenias, and other causes.
The marrow is the principal site of blood cell formation. In the normal adult, daily marrow production is approximately 2.5 billion red cells, 2.5 billion platelets, and 1 billion granulocytes per kilogram of body weight. Rates of cell production vary according to demand and can range from nearly zero to many times normal. Kinetic studies of marrow cells, using radioisotopes and in vitro cultures, have shown that cell lineages consist mainly of maturing cells with finite functional life spans. Sustained cellular production, however, depends on pools of primordial cells capable of both differentiation and self-replication. The most primitive pool consists of pluripotential lymphohematopoietic stem cells with the capacity for continuous self-renewal, that is, hematopoietic stem cells (HSCs). More mature pools include (a) progenitor cells that can be identified by in vitro culture techniques or by identification of cluster of differentiation (CD) markers and can ...