CASIN and AMD3100 enhance endothelial cell proliferation, tube formation and sprouting

Abstract

Endothelial dysfunction is prominent in atherosclerosis, hypertension, diabetes, peripheral and cardiovascular diseases, and stroke. Novel therapeutic approaches to these conditions often involve development of tissue-engineered veins with ex vivo expanded endothelial cells. However, high cell number requirements limit these approaches to become applicable to clinical applications and highlight the requirement of technologies that accelerate expansion of vascular-forming cells. We have previously shown that novel small molecules could induce hematopoietic stem cell expansion ex vivo. We hypothesized that various small molecules targeting hematopoietic stem cell quiescence and mobilization could be used to induce endothelial cell expansion and angiogenesis due to common origin and shared characteristics of endothelial and hematopoietic cells. Here, we have screened thirty-five small molecules and found that CASIN and AMD3100 increase endothelial cell expansion up to two-fold and induce tube formation and ex vivo sprouting. In addition, we have studied how CASIN and AMD3100 affect cell migration, apoptosis and cell cycle of endothelial cells. CASIN and AMD3100 upregulate key endothelial marker genes and downregulate a number of cyclin dependent kinase inhibitors. These findings suggest that CASIN and AMD3100 could be further tested in the development of artificial vascular systems and vascular gene editing technologies. Furthermore, these findings may have potential to contribute to the development of alternative treatment methods for diseases that cause endothelial damage.

Keywords: Artificial vein; Endothelial cells; Sprouting; Tissue engineering; Tube formation.