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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 (yellow marrow) replace hematopoietic cells in the bones of the hands, feet, legs, and arms. Fat comprises approximately 50 percent of red marrow in the adult. Further fatty replacement of the red marrow continues slowly with aging, but hematopoiesis can be expanded when demand for blood cells is increased.
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; a thin basement membrane; and adventitial reticular cells that are progenitors of chondrocytes, osteoblasts and adipocytes. Stem cells can leave and reenter marrow as part of their normal circulation.
Hematopoiesis, the proliferation and differentiation of stem cells and their progeny in the intersinus spaces, is controlled by a complex array of stimulatory and inhibitory cytokines, cell–cell contacts, and interactions with the extracellular matrix. 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 hematopoietic system also 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; 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; C/EBP, CCAAT/enhancer-binding protein; CFU-E, colony forming unit–erythroid; CFC-G, colony-forming cell-granulocyte; CXCL12/SDF1, stromal cell-derived factor; dpc, days postcoitum; EBI, erythroblastic island; ECM, extracellular matrix; ELAM, endothelial leukocyte adhesion molecule; EPO, erythropoietin; FN, fibronectin; GAG, glycosaminoglycan; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GMP, granulocyte-macrophage progenitor; HGF, hepatocyte growth factor; HIF, hypoxia-inducible factor; HSC, pluripotent hematopoietic stem cell; ICAM, intercellular adhesion molecule; IHH, Indian hedgehog family of proteins; IL, interleukin; LFA, lymphocyte function antigen; MAdCAM, mucosal addressin cell adhesion molecule; M-CSF, macrophage colony-stimulating factor; MEP, megakaryocytic-erythroid progenitor; MIP, macrophage inflammatory protein; MMP, matrix metalloproteinase; MPP, multipotential pluripotential progenitor; MSC, mesenchymal stem cell; NFAT, nuclear factor of activated T cells; NK, natural killer; OPG, osteoprotegerin; PDGF, platelet-derived growth factor; PECAM, platelet endothelial cell adhesion molecule; PPAR, peroxisome proliferator-activated receptor; ProEBs, proerythroblasts; PSGL, P-selectin glycoprotein ligand; RANK, receptor activator of nuclear factor-κB; Rb, retinoblastoma tumor-suppressor protein; SCF, stem cell factor; Siglecs, sialic acid-binding immunoglobulin (Ig)-like lectins; SP, side population; TGF-β, transforming growth factor-β; TLR, toll-like receptor; TNF-α, tumor necrosis factor-α; TPO, thrombopoietin; TRAP, tartrate-resistant acid phosphatase; TSP, thrombospondin; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth ...