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.
Degree
M.S.