Growth factors induce the improved cardiac remodeling in autologous mesenchymal stem cell-implanted failing rat hearts

Abstract

Therapeutically delivered mesenchymal stem cells (MSCs) improve ventricular remodeling. However, the mechanism underlying MSC cardiac remodeling has not been clearly determined. Congestive heart failure (CHF) was induced in rats by cauterization of the left ventricular free wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 d after injury. Ten weeks later, when compared with sham operation, CHF significantly increased nucleus mitotic index, capillary density, and expression of insulin-like growth factor 1, hepatocyte growth factor and vascular endothelial growth factor in the border zone (P<0.01) and decreased each of them in the remote myocardium (P<0.05 or P<0.01). MSC implantation in CHF dramatically elevated expression of these growth factors in the remote myocardium and further elevated their expression in the border zone when compared with CHF without MSC addition (P<0.05 or P<0.01). This was paralleled by a higher nucleus mitotic index and a significantly increased capillary density both in the remote myocardium and in the border zone, and by a lower percentage of area of collagen and a higher percentage of area of myocardium in the border zone (P<0.05 or P<0.01), and cardiac remodeling markedly improved. Autologous MSC implantation promoted expression of growth factors in rat failing myocardium, which might enhance cardiomyogenesis and angiogenesis, and improved cardiac remodeling.