Model of support for hematopoietic stem cells by osteoblasts. The stem cell niche is composed of several members of the BMSC system, all derived from a common mesenchymal stem cell. Recent studies demonstrate that endosteal osteoblasts and their precursors play a critical role in the creation of a stem cell niche and thereby likely regulate stem cell maintenance, proliferation, and maturation. Central to this hypothesis is the demonstration that osteoblast-expressed regulatory components that influence stem cell function are likely to include cell-cell receptors, soluble and cell surface–associated cytokines, and growth factors. Each of these factors—those known and those yet to be determined—are likely influenced by mechanical, systemic (eg, PTH), and local (eg, BMPs, Ang-1) signals that regulate osteoblastic function. Furthermore, reciprocal cooperation between stem cells and osteoblasts and other cell types is likely to play a key role in the establishment and maintenance of the stem cell niche in the bone marrow.