Induction of initial steps of angiogenic differentiation and maturation of endothelial cells by pericytes in vitro and the role of collagen IV

Activation of endothelial cells and recruitment of mural cells define critical steps during the formation of stable vascular elements. Both events are reflected by cocultures of endothelial cells and isolated murine pericyte-like cells and define a versatile platform for the analysis of distinct steps during the angiogenic process in vitro. Isolated pericyte-like cells promote the survival of endothelial cells, induce the assembly of endothelial cells as well as establish direct contacts with forming endothelial alignments. More importantly, they also induce characteristic steps of maturation including the assembly of stable cell-cell junctions, deposition of basement membrane-like matrices and local formation of a central lumen. The presence of pericyte-like cells induces the secretion of extracellular matrices enriched in collagen IV by endothelial cells, which improves endothelial tube formation and provides the adhesive substrate for mural cell recruitment. Collagen-binding integrins contribute differentially to the process, with α1β1 involved in the adhesion of pericyte-like cells to collagen IV and α2β1 mainly involved in endothelial cord formation. These data indicate that pericyte-like cells are essential for the survival of endothelial cells, the efficient formation of endothelial alignments as well as initial steps of maturation of capillary-like structures.