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

// Yan-Ling Zeng 1, 2, * , Hao Zheng 1, * , Qiu-Ru Chen 1, * , Xiao-Hong Yuan 1 , Jin-Hua Ren 1 , Xiao-Feng Luo 1 , Ping Chen 1 , Zhe-Yao Lin 2 , Shao-Zhen Chen 1 , Xue-Qiong Wu 1 , Min Xiao 1 , Yong-Quan Chen 1 , Zhi-Zhe Chen 1 , Jian-Da Hu 1, * , Ting Yang 1, * 1 Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China 2 Department of Hematology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping 353000, P. R. China * These authors are regarded as co-first author Correspondence to: Ting Yang, email: yang.hopeting@gmail.com Jian-Da Hu, email: drjiandahu@163.com Keywords: microRNA-21, lentiviral vector, bone marrow derived mesenchymal stem cell, anthracycline, cardiac damage Received: November 23, 2016     Accepted: February 08, 2017     Published: March 16, 2017 ABSTRACT Objective: 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. Methods: 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. Results: 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. Conclusion: 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.