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SUMMARY
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.
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Acronyms and Abbreviations
AGM, aorta-gonad-mesonephros; bFGF, basic fibroblast growth factor; SBFU-E, burst-forming unit–erythroid; BMP, bone morphogenetic protein; CAR cells, CXCL12-abundant reticular cells; CD, cluster of differentiation; C/EBP, CCAAT enhancer binding protein; CFU-E, colony forming unit–erythroid; CFU-GEMM, colony-forming unit–granulocyte-erythroid- monocyte-macrophage; CFU-GM, colony-forming units–granulocyte-macrophage; CLP, common lymphoid progenitor; CMP, common myeloid progenitor; CXCL, CXC ligand; CXCL12, C-X-C chemokine CXCL12/stromal cell-derived factor 1; EBP, erythroblastic islands; ECMs, extracellular matrix proteins; ELP, early lymphoid progenitors; EMP, erythroblast-macrophage protein; EPO, erythropoietin; FLT-3, FMS-like tyrosine kinase 3; FN, fibronectin; FOG, friend of GATA; GAG, glycosaminoglycan; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; HCAM, homing cell adhesion molecule; HEVs, high endothelial venules; HGF, hepatocyte growth factor; HIFα, hypoxia-inducible factor α; HPC, hematopoietic progenitor cell; HSC-hematopoietic stem cell; ICAM, intercellular adhesion molecule; IHH, Indian hedgehog proteins; IL, interleukin; Lep, Leptin; LFA, lymphocyte function-associated antigen; MAdCAM, mucosal addressin cell adhesion molecule; M-CSF, macrophage colony-stimulating factor; MEP, megakaryocyte-erythroid progenitor; MIP-2/CXCL2, macrophage inhibitory protein-2; MMP-9, matrix metalloproteinase-9; MSC, mesenchymal stem cell; NFAT, nuclear factor of activated T cells; NK, natural killer; OPG, osteoprotegerin; OPN, osteopontin; PDGF, platelet-derived growth factor receptor α; ...