MSCs transfected with hepatocyte growth factor or vascular endothelial growth factor improve cardiac function in the infarcted porcine heart by increasing angiogenesis and reducing fibrosis

Abstract

BackgroundCell transplantation and gene therapy have been demonstrated to have beneficial effects after a myocardial infarction (MI). Here, we used a large animal model of MI to investigate the beneficial effects of mesenchymal stem cells (MSCs) transfected with hepatocyte growth factor (HGF) or vascular endothelial growth factor (VEGF) genes. MethodsA porcine MI model was created by balloon occlusion of the distal left anterior descending artery for 90min followed by reperfusion. At 1week after MI, the pigs were infused via the coronary vein with saline (n=8), MSCs+AdNull(n=8), MSC+VEGF(n=10), or MSC+HGF(n=10). Cardiac function and myocardial perfusion were evaluated by using echocardiography and gated cardiac perfusion imaging before and 4weeks after transplantation. Morphometric and histological analyses were performed. ResultsAll cell-implanted groups had better cardiac function than the saline control group. There were further functional improvements in the MSC+HGF group, accompanied by smaller infarct sizes, increased cell survival, and less collagen deposition. Blood vessel densities in the damaged area and cardiac perfusion were significantly greater in the MSC+AdNull group than in the saline control group, and further increased in the MSC+VEGF/HGF groups. Tissue fibrosis was significantly less extensive in the MSC and MSC+VEGF groups than in the saline control group and was most reduced in the MSC+HGF group. ConclusionMSCs (alone or transfected with VEGF/HGF) delivered into the infarcted porcine heart via the coronary vein improved cardiac function and perfusion, probably by increasing angiogenesis and reducing fibrosis. MSC+HGF was superior to MSC+VEGF, possibly owing to its enhanced antifibrotic effect.