IN MAMMALS, HEMATOPOIESIS shifts to the bone marrow in late embryogenesis, coincident with the appearance of a marrow cavity.(1) There hematopoiesis is sustained throughout adult life unless forced out of the bone marrow into extramedullary sites by pathological conditions. All hematopoietic lineages arise from the hematopoietic stem cell (HSC), and maintenance of HSC self-renewal and differentiation are critically dependent on the presence of a supportive microenvironment, or niche. The existence of such a niche within the bone marrow was first postulated by Schofield,(2) and the vital role of the bone marrow microenvironment has been convincingly shown in the three decades since.

The marrow microenvironment is comprised of cells of multiple lineages, including fibroblast-like cells, adipocytes, osteoblasts, and endothelial cells. Recent studies have begun to highlight the contributions of individual lineages to the hematopoietic niche, with the greatest weight of evidence thus far in support of important roles for osteoblasts and the vasculature.(3–5) In humans, CD146+ subendothelial cells have been reported to serve as skeletal progenitors capable of generating cells that organize a hematopoietic microenvironment on transplantation.(6) Subsequent studies have shown that the endosteal surface is rich in vasculature with close approximation of osteoblasts and vessel walls.(7, 8) In trabecular bone, it is unlikely that there are physically distinct endosteal and perivascular/vascular niches, although the functional roles of osteoblasts and vascular cells may well differ. This review will focus specifically on the role of cells of the osteoblast lineage within the bone marrow niche. In particular, we will examine the contribution of osteoblasts in supporting hematopoietic stem cells and contrast this with how distinct stages of osteoblast precursors support developing