The overexpression of miR-378 promotes the therapeutic effects of bone marrow mesenchymal stem cell transplantation on myocardial infarction / 中国组织工程研究

ABSTRACT

BACKGROUND: Recently, miR-378 has been shown to modulate the anti-hypoxia capacity of bone marrowmesenchymal stem cells (BMSCs) and reduce cell apoptosis under hypoxic conditions.OBJECTIVE: To investigate the benefits of miR-378-upregulated BMSC transplantation in a rat model of acutemyocardial infarction.METHODS: Primary rat BMSCs were cultured in vitro. Until passage 3, the cells were infected with the lentiviruscarrying synthetic miR-378 gene fragments. A rat model for acute myocardial infarction was constructed by ligatingthe left anterior descending artery. Thereafter, the animals were randomly assigned to three groups control group(n=10), BMSCnull group (n=16) and BMSCmiR-378 group (n=16). In the latter two groups, 50 μL of normal salinecontaining 1×107 empty virus-transfected or miR-378-transfected BMSCs was injected into the region of myocardialinfarction, respectively. Only 50 μL of normal saline was injected in the control group. Twenty-four hours later, theapoptosis of transplanted BMSCs was evaluated with TUNEL, and expression level of vascular endothelial growthfactor and transforming growth factor-β was detected using western blot assay. Four weeks after treatment, the leftventricular function of rats was assessed by echocardiography, and then histological and molecular biology analyseswere performed.RESULTS AND CONCLUSION: At 24 hours postoperatively, there were less apoptotic BMSCs and higher expressionlevels of vascular endothelial growth factor and transforming growth factor-β in the BMSCmiR-378 group than in theBMSCnull group (n=6, P < 0.001). Four weeks later, there were more transplanted BMSCs and BMSCs-derivedcardiomyocytes in the BMSCmiR-378 group than the BMSCnull group (n=10, P < 0.001). Moreover, increased new vesseldensity (P < 0.001), decreased infarcted area (P < 0.001), preserved left ventricular ejection fraction (P < 0.05), reducedleft ventricular end-diastolic volume (P < 0.05) were found in the BMSCmiR-378 group, compared with the other two groups.The above parameters were better in the BMSCnull group than the control group (P < 0.05). Overall, the upregulation ofmiR-378 could enhance the capability of BMSCs against hypoxia, and consequently promote myocardial repair afterimplantation, providing a new strategy for cell therapy of myocardial infarction.