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

Abstract

ObjectiveWe 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.MethodsSprague-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.ResultsUsing 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.ConclusionThese 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.

Circadian MicroRNAs in Cardioprotection

“…However, these results were not reproduced in subsequent studies [37], emphasizing our current challenges in the therapeutic use of microRNAs. In fact, another study on bone marrow-derived mesenchymal stem cells found that overexpressing miR-21 efficiently repaired myocardial damage in rats [64]. …”

“…Recent studies indicate that miR-21 also reduces hydrogen peroxide-induced apoptosis in cardiac stem cells through PTEN/PI3K/AKT signaling [63]. Moreover, bone marrow-derived mesenchymal stem cells overexpressing miR-21 efficiently repair myocardial damage in rats [64]. Interestingly, HIF1A was identified as an upstream transcriptional regulator of miR-21[18].…”

Inhibition of miR‐21 alleviated cardiac perivascular fibrosis via repressing EndMT in T1DM

“…miR‐21 participates in the process of angiogenesis and repair of inflammation or ischaemic injury by reducing NF‐κB or through PTEN/AKT/ERK1‐VEGF pathway . Excessive expression of miR‐21 in bone marrow‐derived mesenchymal stem cells can effectively repair myocardial injury in rats . In the upstream, miR‐21 was regulated by HIF1A, binding together with PER2, which is vital for regulating HIF1A target genes, in hypoxia …”

Bone tissue engineering: Adult stem cells in combination with electrospun nanofibrous scaffolds

“…They are spindle‐shaped nucleated cells with multi‐lineage differentiation potential and immune‐modulating ability which most broadly studied for therapeutic potentials. Indeed, BM‐MSCs have been considered as the gold standard for clinical applications (Batsali et al, ), because they are easily extractable, survive better after transplantation and show weak immunogenicity (Husak & Dworzak, ; Liu et al, ; Shin et al, ; Tsuji et al, ; Zeng et al, ). In fact, BM‐MSCs are represented as the cells of origin of osteosarcoma while they are capable of dividing into one of several mesenchymal phenotypes such as osteoblasts, chondrocytes, myocytes, marrow stromal cells, tendon‐ligament fibroblasts, and adipocytes (Caplan & Dennis, ; Tsuji et al, ; He et al, ).…”