Molecular mechanisms controlling endothelial cell-pericyte tube coassembly during vascular morphogenesis

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] From the onset the goal of this thesis work was to determine the role that a novel class of growth factors, i.e. hematopoietic cytokines, was playing in the development of blood vessels both through the processes of vasculogenesis and angiogenesis. To such an end, multiple combinations of hematopoietic cytokines were assessed for their ability to promote EC tube formation, from which the combination of three- SCF, IL-3 and SDF-1[alpha]- were determined to be synergistically acting factors that had the ability to support vascularization. Further, was to determine the molecular role that support cells, such as pericytes, are playing in the stabilization of the vasculature. It has long been known that pericytes are the primary support cells of the microvascular beds, and that disrupted pericyte recruitment leads to a mispatterned, disrupted vasculature. Therefore the molecular role that pericytes are playing to carry out this function becomes critically important. We hypothesized that pericyte recruitment to the endothelium would be required for proper formation of the vascular basement membrane; therefore novel in vitro systems of EC-pericyte tube coassembly, based on signals driven by hematopoietic cytokines, were developed.