Bone marrow-derived mesenchymal stem cells overexpressing MiR-21 efficiently repair myocardial damage in rats

• Published in: Oncotarget 2017-04, Vol.8 (17), p.29161-29173
• Main Authors: Zeng, Yan-Ling, Zheng, Hao, Chen, Qiu-Ru, Yuan, Xiao-Hong, Ren, Jin-Hua, Luo, Xiao-Feng, Chen, Ping, Lin, Zhe-Yao, Chen, Shao-Zhen, Wu, Xue-Qiong, Xiao, Min, Chen, Yong-Quan, Chen, Zhi-Zhe, Hu, Jian-Da, Yang, Ting
• Format: Article
• Language: English
• Subjects: Animals; Bone Marrow - metabolism; Cell Differentiation; Cells, Cultured; Humans; Mesenchymal Stem Cells - metabolism; MicroRNAs - metabolism; Myocardium - pathology; Rats; Rats, Sprague-Dawley; Research Paper; Transfection
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.16254

We investigated the ability of bone marrow derived mesenchymal stem cells (BMSCs) overexpressing microRNA-21 (miR-21) to repair cardiac damage induced by anthracyclines in rats. Sprague-Dawley (SD) rats of 2~3 weeks old were selected to isolate and culture BMSCs. A lentivirus harboring pLVX-miR-21 was generated and transfected into rat BMSCs. The rats were assigned into an untreated negative control group, and groups injected with adriamycin alone or with adriamycin followed by BMSCs, pLVX-BMSCs or pLVX-miR-21-BMSCs (n = 10 each). Proliferation and migration of cells were detected by cholecystokinin-8 (CCK- 8) and transwell. MiR-21 expression, mRNA expressions of B cell lymphoma 2 (Bcl2), BAX (BCL-2-associated X protein) and vascular endothelial growth factor (VEGF) were tested by qRT-PCR. Western blotting was applied to detect protein expressions of Bcl-2, Bax and VEGF. Using CCK- 8 and transwell assays, we found that pLVX-miR-21-BMSCs, which overexpressed miR-21, exhibited greater proliferation and migration than untransfected BMSCs or pLVX-BMSCs. Ultrasonic cardiograms and immunohistochemical analysis demonstrated that among the five groups, the pLVX-miR-21-BMSC group exhibited the most improved heart function and enhanced angiogenesis. Moreover, the pLVX-miR-21-BMSC group showed enhanced expression of Bcl-2, VEGF and Cx43 and reduced expression of Bax, BNP and troponin T. These findings suggest miR-21 overexpression enhanced the proliferation, invasiveness and differentiation of BMSCs as well as expression of key factors (Bcl-2, VEGF and Bax) essential for repairing the cardiac damage induced by anthracyclines and restoring heart function.