Mesenchymal stem cells overexpressing MiR-126 enhance ischemic angiogenesis via the AKT/ERK-related pathway

Background: This study was designed to examine whether transplantation of mesenchymal stem cells (MSCs) overexpressing miR-126 enhances angiogenesis in the infarcted myocardium of mice. Methods: MSCs were harvested from mice using density gradient centrifugation and adherent culture. MSCs were transfected with lentiviral vectors carrying mature miR-126. Mice models of myocardial infarction were established by ligation of coronary artery. The ligated animals were randomly divided into three groups ( 15 in each) and after two weeks, were intramyocardially injected at the heart infarct zone with miR-126-transfected MSCs (the miR-126-MSCs group), MSCs (the MSCs group), or medium (the PBS group). Six weeks later, histological study and echocardiographic assessment were performed. Results: Capillary density of the infarcted region was significantly improved in the miR-126-MSCs group compared to the MSC group and the PBS group (both p < 0.01). Western blot showed that ERK1, PERK1, AKT and pAKT gene were dramatically enhanced in the miR-126-MSC group compared to the MSC group and the PBS group (both p < 0.05). Echocardiography showed MiR-126 led to a sustained improvement in cardiac function for at least six weeks at the injected area, as assessed by left ventricular ejection fraction and fraction of shortening. Conclusions: Transplantation of MSCs transfected with miR-126 can improve angiogenesis and cardiac function in the infarcted area of the hearts of mice, which may be due to stimulation of the AKT/ERK-related pathway. (Cardiol J 2011; 18, 6: 675-681)