Enhanced Cardioprotection by Human Endometrium Mesenchymal Stem Cells Driven by Exosomal MicroRNA-21

作者：Kan Wang, Zhi Jiang, Keith A. Webster, Jinghai Chen, Hengxun Hu, Yu Zhou, Jing Zhao, Lihan Wang, Yingchao Wang, Zhiwei Zhong, Cheng Ni, Qingju Li, Charlie Xiang, Ling Zhang, Rongrong Wu, Wei Zhu, Hong Yu, Xinyang Hu, Jianan Wang · 发表于：Stem Cells Translational Medicine · 年份：2016 · DOI：10.5966/sctm.2015-0386 · 被引用次数：277 · 研究领域：Extracellular vesicles in disease、MicroRNA in disease regulation、Circular RNAs in diseases

Our group recently reported positive therapeutic benefit of human endometrium-derived mesenchymal stem cells (EnMSCs) delivered to infarcted rat myocardium, an effect that correlated with enhanced secretion of protective cytokines and growth factors compared with parallel cultures of human bone marrow MSCs (BMMSCs). To define more precisely the molecular mechanisms of EnMSC therapy, in the present study, we assessed in parallel the paracrine and therapeutic properties of MSCs derived from endometrium, bone marrow, and adipose tissues in a rat model of myocardial infarction (MI). EnMSCs, BMMSCs, and adipose-derived MSCs (AdMSCs) were characterized by fluorescence-activated cell sorting (FACS). Paracrine and cytoprotective actions were assessed in vitro by coculture with neonatal cardiomyocytes and human umbilical vein endothelial cells. A rat MI model was used to compare cell therapy by intramyocardial injection of BMMSCs, AdMSCs, and EnMSCs. We found that EnMSCs conferred superior cardioprotection relative to BMMSCs or AdMSCs and supported enhanced microvessel density. Inhibitor studies indicated that the enhanced paracrine actions of EnMSCs were mediated by secreted exosomes. Analyses of exosomal microRNAs (miRs) by miR array and quantitative polymerase chain reaction revealed that miR-21 expression was selectively enhanced in exosomes derived from EnMSCs. Selective antagonism of miR-21 by anti-miR treatment abolished the antiapoptotic and angiogenic effects of EnMSCs with p...