Endothelial to Mesenchymal Transformation in Cardiovascular Tissue Engineering

Abstract

We envision the use of blood-derived endothelial progenitor cells (EPCs) to repair cardiovascular defects, including cardiac valve defects. To pursue this, we are studying growth and differentiation pathways in normal cardiac valve endothelium. Two of our studies have shown that valve endothelial cells from adult tissue can recapitulate processes that occur during valve development. These pathways involve TGF-β-induced endothelial to mesenchymal transformation (EMT) and VEGF-induced proliferation. In support of the concept of using blood-derived EPCs to create tissue-engineered heart valves, we have shown that EPCs respond, like valve endothelial cells, to VEGF and TGF-b when seeded on 3-dimensional biodegradable scaffolds. We hypothesize that human EPCs, expanded ex vivo, can be induced to behave as valve endothelial cells and thereby manipulated, via tissue engineering processes, to create viable long-lived tissue valve substitutes.