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

Abstract

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 ERK(1), pERK(1), 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.