Prospect of Stem Cells in Bone Tissue Engineering: A Review

Figure 3

How MSCs make it to bone marrow. During development, the primitive bone marrow stroma includes skeletal progenitors that originate outside of the marrow cavity (primitive periosteum and perichondrium) and invade the forming cavity along blood vessels. Similar dynamic interactions with ingrowing blood vessels are reproduced in transplants of human MSCs and are probably the basis for the perisinusoidal position of MSCs in the intact postnatal bone marrow. Recruitment of mesenchymal cells to a mural cell fate (and a subendothelial position), a general phenomenon in development and organ growth, is mediated by endothelial cell (EC) derived PDGF-BB, which signals through PDGFR-β expressed on mesenchymal cells (and MSCs). Presumptive mural cells (as well as human and mouse bone marrow MSCs) produce Ang-1, which is crucial for the integrity, survival, and remodeling of vascular lattices. Ang-1 also induces quiescence of hematopoietic stem cells (HSCs). Both mural cells and endothelial cells are induced to mitotic quiescence by active TGF-β1, which is released through proteolytic cleavage of the latent form at sites of mural cell, endothelial cell contacts. Reprinted by permission from Macmillan Publishers Ltd., Nature Medicine, Bianco et al. [46], copyright © 2013.