Enhanced cardioprotection by human endometrium mesenchymal stem cells driven by exosomal MicroRNA-21

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, Jian’An Wang

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

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 (Ml). 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 Ml 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 parallel effects on phosphatase and tensin homolog (PTEN), a miR-21 target and downstream Akt. The results of the present study confirm the superior cardioprotection by EnMSCs relative to BMMSCs or AdMSCs and implicates miR-21 as a potential mediator of EnMSC therapy by enhancing cell survival through the PTEN/Akt pathway. The endometrium might be a preferential source of MSCs for cardiovascular cell therapy.

Original languageEnglish (US)
Pages (from-to)209-222
Number of pages14
JournalStem Cells Translational Medicine
Volume6
Issue number1
DOIs
StatePublished - Jan 2017

Keywords

  • Adipose
  • Bone marrow
  • Cell therapy
  • Endometrium
  • Mesenchymal stem cells
  • Myocardial infarction

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Wang, K., Jiang, Z., Webster, K. A., Chen, J., Hu, H., Zhou, Y., Zhao, J., Wang, L., Wang, Y., Zhong, Z., Ni, C., Li, Q., Xiang, C., Zhang, L., Wu, R., Zhu, W., Yu, H., Hu, X., & Wang, JA. (2017). Enhanced cardioprotection by human endometrium mesenchymal stem cells driven by exosomal MicroRNA-21. Stem Cells Translational Medicine, 6(1), 209-222. https://doi.org/10.5966/sctm.2015-0386