Mesenchymal stem cells and neovascularization: Role of platelet-derived growth factor receptors: Angiogenesis Review Series

Abstract

Introduction The vascular endothelial growth factor/platelet-derived growth factor super-family of ligands and receptors Vascular endothelial growth factor ligands Platelet-derived growth factor ligands Vascular endothelial growth factor receptors Platelet-derived growth factor receptors Role of platelet-derived growth factor receptors in regulating the MSC fate MSCs utilize a novel vascular endothelial growth factor/platelet-derived growth factor receptor signalling mechanism Regulation of vascular endothelial growth factor/platelet-derived growth factor receptor signalling MSCs and the vasculature Differentiation of MSCs towards endothelial cells Differentiation of MSCs towards vascular smooth muscle lineages MSCs during vascular injury Contribution of MSCs to vasculogenesis MSCs during ischaemic myocardial tissue regeneration Involvement of MSCs during tumour vasculogenesis Summary There is now accumulating evidence that bone marrow-derived mesenchymal stem cells (MSCs) make an important contribution to postnatal vasculogenesis, especially during tissue ischaemia and tumour vascularization. Identifying mechanisms which regulate the role of MSCs in vasculogenesis is a key therapeutic objective, since while increased neovascularization can be advantageous during tissue ischaemia, it is deleterious during tumourigenesis. The potent angiogenic stimulant vascular endothelial growth factor (VEGF) is known to regulate MSC mobilization and recruitment to sites of neovascularization, as well as directing the differentiation of MSCs to a vascular cell fate. Despite the fact that MSCs did not express VEGF receptors, we have recently identified that VEGF-A can stimulate platelet-derived growth factor (PDGF) receptors, which regulates MSC migration and proliferation. This review focuses on the role of PDGF receptors in regulating the vascular cell fate of MSCs, with emphasis on the function of the novel VEGF-A/PDGF receptor signalling mechanism. © 2007 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.