Figure 3. Perivascular Niche of Mesenchymal and Hematopoietic Stem Cells.

In the bone marrow, both MSCs and HSCs reside in the perivascular niche. The endothelial sinusoid is surrounded by MSCs identified as pericytes and a stromal subpopulation that can be further identified by their expression of nestin and/or leptin receptors. CAR cells are MSCs characterized by high expression of the chemokine CXCL12, a chemoattractant for CXCR4-expressing HSCs. Sympathetic neural fibers also connect with the niche and may provide negative proliferative signals. E-selectin is expressed exclusively on the endothelial cells of the niche and can bind HSCs expressing an appropriate ligand. ESC-1 is shown here as a candidate ligand, the binding of which to E-selectin is required for circulating HSCs to attach and roll on the sinusoidal endothelium before their firm attachment and egress. The attachment to E-selectin–expressing endothelium induces HSC proliferation, self-renewal and chemo- and radiosensitivity. HSCs also reside close to the bone endosteal surface (a more hypoxic environment) and may receive instructive cues from osteoblasts and osteoprogenitors. Reprinted by permission from Macmillan Publishers Ltd: Nature Medicine¹²⁷ copyright 2012.