Functional differences between pericytes and vascular smooth muscle cells during vascular morphogenesis

Abstract

During vascular morphogenic events, mural cells are recruited to developing endothelial tubes to aid in stabilization and maturation of the new vessels. There are two known types of mural cells, pericytes and vascular smooth muscle cells (VSMCs). Their different locations within the vasculature (capillaries versus larger vessels, respectively) suggest that different signals may be responsible for recruiting each cell type. Platelet-­‐derived growth factor (PDGF) is released from endothelial cells (ECs) during morphogenic events and has been shown to influence mural cell functions. In this study, I investigated the ability of PDGF isoforms to regulate pericyte and VSMC invasiveness and subsequent effects on EC monolayer stability and tube sprouting. Using novel cell-­‐invasion systems developed during this research, I show that PDGF isoforms that bind to PDGFRβ induce pericyte, but not VSMC invasion. Coculture studies revealed that the invasive behavior of pericytes is critical to both EC stability and sprouting. When ECs were seeded as a monolayer on top of 3D collagen gels containing pericytes, monolayer stability was enhanced compared to EC monolayers seeded alone or with VSMCs. Coculture studies also revealed that EC sprouting was sustained when pericytes were present compared to EC only cultures or EC/VSMC cocultures. Results from this work define functional differences between pericytes and VSMCs during vascular morphogenesis.