1. Exogenous miRNA-146a Enhances the Therapeutic Efficacy of Human Mesenchymal Stem Cells by Increasing Vascular Endothelial Growth Factor Secretion in the Ischemia/Reperfusion-Injured Heart.
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Seo, Hyang-Hee, Lee, Se-Yeon, Lee, Chang Youn, Kim, Ran, Kim, Pilseog, Oh, Sekyung, Lee, Hojin, Lee, Min Young, Kim, Jongmin, Kim, Lark Kyun, Hwang, Ki-Chul, and Chang, Woochul
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MICRORNA ,MESENCHYMAL stem cells ,TREATMENT effectiveness ,VASCULAR endothelial growth factors ,NEUROFIBROMIN ,THERAPEUTICS - Abstract
Adult stem cells have been studied as a promising therapeutic modality for the functional restoration of the damaged heart. In the present study, a strategy for enhancing the angiogenic efficacy of human mesenchymal stem cells (hMSCs) using micro-RNA was examined. We investigated whether micro-RNA-146a (miR-146a) influences the secretion of vascular endothelial growth factor (VEGF) and angiogenesis of MSCs. Our data indicated that miR-146a-transfected hMSCs (hMSC
miR-146a ) decreased the expression of neurofibromin 2, an inhibitor of p21-activated kinase-1 (PAK1).miR-146a also increased the expression of Ras-related C3 botulinum toxin substrate 1 and PAK1, which are known to induce VEGF expression, and the formation of vascular branches was increased in hMSCmiR-146a compared to hMSCs treated with VEGF. VEGF and p-Akt were increased in hMSCmiR-146a . Furthermore, injection of hMSCmiR-146a after ischemia/reperfusion (I/R) injury led to a reduction of fibrosis area and increased VEGF expression, confirming the regenerative capacity such as reparative angiogenesis in the infarcted area. Cardiac functions in I/R injury were improved following injection of hMSCmiR-146a compared to the I/R group. Taken together, these data suggest that miR-146 is a novel microRNA that regulates VEGF expression, and its use may be an effective strategy for enhancing the therapeutic efficacy of hMSC transplantation into the I/R-injured heart. [ABSTRACT FROM AUTHOR]- Published
- 2017
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