Abstract 17107: Induced Vascular Progenitor Cells Derived From Endothelial Cells Stimulate Coronary Collateral Growth
Although regenerative medicine has great potential in stimulating vascular growth in the heart, there have been mixed results and the ideal cell type for therapy has not been resolved. Induced pluripotent cells (iPSCs) show promise, because they can be autologous, but they suffer from the problem of potential tumor formation. To circumvent this problem, we reasoned that reprogramming cells to a progenitor-type cell, rather than to pluripotency, but would reduce the chances for tumor formation; yet still enable their application in stimulating coronary collateral growth in a rat model of repetitive ischemia. Accordingly, we reprogrammed endothelial cells (EC(s)) to “induced vascular progenitor cell(s)” (iVPC(s)), which should remain committed to a vascular lineage. We hypothesized that these cells would better stimulate coronary collateral growth than fully reprogrammed iPSCs because the latter can differentiate into various cell types other than vascular lineage. Rat vascular ECs were transduced with Oct4, Klf4, Sox2 and c-Myc. A population of reprogrammed cells expressing pluripotent markers, Oct4, SSEA-1, Rex1 and AP and markers of hemangioblasts, CD133, Flk1, c-kit were generated. These cells were named iVPCs, because they remained committed to vascular lineage and could differentiate into vascular ECs or vascular smooth muscle cells in vitro. iVPCs demonstrated better in vitro angiogenic potential (tube network on 2D culture, tube formation in serum reduced matrigel) than native ECs. In contrast to iPSCs, iVPCs had far less risk of teratoma formation. When iVPCs were implanted into rat myocardium, they engrafted into the blood vessels, increased coronary collateral flow measured by microspheres and improved cardiac function during coronary occlusion measured by echocardiography better than iPSCs or sham treatment (all difference were significant at P<0.05). Thus we successfully reprogrammed ECs into iVPCs. iVPCs had a better effect on coronary collateral growth and cardiac function during a coronary occlusion in vivo than iPS cells did. We conclude that “induced vascular progenitor cells,” generated by partial reprogramming of ECs, are an ideal cell type for regenerative therapy to stimulate coronary collateral growth.
- © 2011 by American Heart Association, Inc.