Platelet-derived growth factor receptors regulate mesenchymal stem cell fate: implications for neovascularization

Importance of the field: Regulating stem cell contributions to vascularization is a challenging goal, but a fundamental aspect of regenerative medicine. Human mesenchymal stem cells retain considerable potential for adult vascular repair and regeneration therapies. They are readily obtained, rapidly proliferate in culture, display a capacity to differentiate towards endothelial or vascular smooth muscle cells, and play an important role in postnatal neovascularization in various tissue contexts. To therapeutically enhance neovascularization during ischemic disease, or inhibit neovascularization during tumorigenesis, an essential prerequisite is to determine the mechanisms which control the recruitment and differentiation of mesenchymal stem cells towards vascular cells. Areas covered in this review: In this review, we describe the current understanding of how PDGF receptors contribute prominently to neovascularization, and play a decisive role in modulating mesenchymal stem cell recruitment and differentiation towards vascular cells. We discuss PDGF receptor-based therapeutic strategies to exploit mesenchymal stem cells during vascular repair and regeneration, and to control pathological neovascularization. Take home message: PDGF receptor signaling is emerging as a critical regulatory mechanism and important therapeutic target, that critically directs the fate of mesenchymal stem cells during postnatal neovascularization.