Abstract 5115: Purified Human Muscle-Derived Pericytes Support Formation of Vascular Structures and Promote Angiogenesis After Myocardial Infarction
We have recently shown that perivascular cells isolated from multiple human tissues represent stem cells endowed with mesodermal lineage potentials, and the injection of multipotent muscle-derived pericytes repair damaged skeletal muscle in vivo. Our current study further demonstrated that transplantation of human muscle-derived pericytes (3.0×105 cells/heart) into the ischemic myocardium of NOD/SCID mice sustains the cardiac function of the infarcted hearts. Here, we tested the hypothesis that purified CD34−/45−/56−/146high pericytes support formation of structures of blood vessels and promote angiogenesis post infarction. To illustrate the potential vessel-forming properties of purified pericytes, pericytes and endothelial cells were co-cultured in Matrigel in vitro, and co-formation of capillary-like structures was observed. To evaluate the angiogenic effect of pericytes in vivo, histological examination was performed two weeks after transplantation. Capillary density was measured by anti-CD31 staining on tissue sections. Capillary density within peri-infarct areas was 43% higher in the pericyte-injected group than in the saline-injected group (P<0.05). Myocardial fibrosis estimated by Masson’s trichrome staining revealed a 38% reduction of the scar area in pericyte-injected hearts when compared to saline-injected hearts. These findings indicated that transplantation of pericytes sustains the cardiac function of the infarcted left ventricle presumably through enhancement of angiogenesis and reduction of myocardial fibrosis. We further examined potential mediators of pericyte-induced cardiac repair in the ischemic micro-environment by culturing pericytes under hypoxic conditions (2.5% oxygen) in vitro for 24 hours. Real-time quantitative PCR analysis showed that vascular endothelial growth factor (VEGF)-related genes, including VEGF165 and VEGF receptor 1 and 2, were significantly up-regulated in the pericyte population. Overall, the data suggested a role of VEGF-regulated angiogenesis on pericyte-mediated cardiac repair. Experiments are being performed to elucidate the potential of pericytes to differentiate into cardiac cell lineages and explore the regulatory mechanisms involved in vivo.