Bone marrow-derived mesenchymal stem cells overexpressing miR-21 efficiently repair myocardial damage in rats
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Yan-Ling Zeng1,2,*, Hao Zheng1,*, Qiu-Ru Chen1,*, Xiao-Hong Yuan1, Jin-Hua Ren1, Xiao-Feng Luo1, Ping Chen1, Zhe-Yao Lin2, Shao-Zhen Chen1, Xue-Qiong Wu1, Min Xiao1, Yong-Quan Chen1, Zhi-Zhe Chen1, Jian-Da Hu1,*, Ting Yang1,*
1Department of Hematology, Fujian Institute of Hematology, Fujian Provincial Key Laboratory of Hematology, Fujian Medical University Union Hospital, Fuzhou 350001, P. R. China
2Department of Hematology, Affiliated Nanping First Hospital of Fujian Medical University, Nanping 353000, P. R. China
*These authors are regarded as co-first author
Ting Yang, email: firstname.lastname@example.org
Jian-Da Hu, email: email@example.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
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.
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