Exosomes derived from miR-133a-3p engineered mesenchymal stem cells promote myocardial repair in rats after acute myocardial infarction

Abstract

Objective: To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats. Methods: UcMSC was amplified and cultured in vitro. Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results: Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P<0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P<0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P<0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P<0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P<0.000 1). Conclusion: Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.