Transplantation of human umbilical vein endothelial cells improves left ventricular function in a rat model of myocardial infarction

Abstract

Although cell-based therapy after myocardial infarction (MI) may be beneficial in improving cardiac dysfunction, the underlying mechanisms remain to be clarified. Since human umbilical vein endothelial cells (HUVEC) harbor the potential for transdifferentiation, we studied the functional effects of HUVEC transplantation in a rat model of MI. HUVEC labeled with BrdU or medium alone were injected into the infarcted area and its margin 4 weeks after ligation of the left coronary artery in cyclosporine-treated rats. BrdU(+) signals could be detected in the area of MI at two weeks and two months after injection only in hearts transplanted with HUVEC. While no signs of transdifferentiation into cardiomyocytes were evident, staining for the rat macrophage marker ED-1, adjacent to or colocalized with BrdU(+) signals, revealed an in.ltration with macrophages and implied the phagocytosis of injected HUVEC. In the vicinity of BrdU(+) signals, the density of CD31(+) microvessels was significantly increased in HUVEC-transplanted as compared to medium-treated hearts after two months. HUVEC transplantation led to improved contractility as assessed by echocardiography and to higher coronary flow rates as well as to improved response to volume strain and catecholamine stress in Langendorff perfused hearts. After MI, transplanted HUVEC persist in the host myocardium and trigger an infiltration with macrophages. The ensuing increase in neovascularization and improvement in global left ventricular function may be attributable to the associated inflammatory response.