中国组织工程研究2017，Vol.21Issue(9)：1390-1396,7.DOI:10.3969/j.issn.2095-4344.2017.09.015
过表达miR-378骨髓间充质干细胞移植治疗心肌梗死
The overexpression of miR-378 promotes the therapeutic effects of bone marrow mesenchymal stem cell transplantation on myocardial infarction
摘要
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.关键词
干细胞/移植/心肌梗死/骨髓间充质干细胞/miR-378/血管新生/心肌梗死面积/左室射血分数分类
医药卫生引用本文复制引用
张秀敏,于波,李学渊..过表达miR-378骨髓间充质干细胞移植治疗心肌梗死[J].中国组织工程研究,2017,21(9):1390-1396,7.基金项目
辽宁省科学技术计划项目(2012225084) （2012225084）
沈阳市科学技术项目(F12-193-9-03、F16-206-9-08) （F12-193-9-03、F16-206-9-08）
辽宁省教育厅科学研究一般项目(L2013316) the Science and Technology Plan of Liaoning Province, No. 2012225084 （L2013316）
the Science and Technology Plan of Shenyang, No. F12-193-9-03, F16-206-9-08 （）
the Scientific Research Project of Liaoning Provincial Department of Education, No. L2013316 （）
