Transformed human brain pericytes enhance endothelial wound healing and angiogenic sprout formation (670.5)

Abstract

We have recently discovered that density‐stressed human brain pericytes transform to a stem cell‐like phenotype; they form spheres that self‐renew and generate daughter cells with varying morphologies. Co‐culture of transformed pericytes with endothelial cells in a scrape wound assay increased the rate of wound healing as compared with non‐transformed co‐cultures. The goal of this study was to identify mechanisms by which transformed pericytes increase the rate of wound healing and to test the hypothesis that transformed pericytes increase the rate of angiogenic sprout formation. To stimulate sprout formation, primary human brain endothelial cells and pericytes were co‐cultured in a collagen matrix with vascular endothelial growth factor. In a scrape wound assay, lipophilic cell membrane dyes (DiO, DiD; Molecular Probes) were used to visualize and track respective cell types. Transformed pericytes increased sprout formation by 2.13 ± 0.08 fold (p<0.05) compared to endothelial cells co‐cultured with non‐transformed pericytes. In the scrape wound assay, both endothelial cells and transformed pericytes were present at the wound edge. In contrast to the non‐transformed co‐cultures, many of the transformed pericytes fused with endothelial cells during wound repair. Cell fusion was positively correlated with a higher rate of wound healing. Transformed pericytes may be a source of stem cell‐like cells with pro‐angiogenic potential.Grant Funding Source: NIH HL10654801