Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22

Yuliang Feng, Wei Huang, Mashhood Wani, Xiyong Yu, Muhammad Ashraf

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Abstract

Mesenchymal stem cells (MSCs) have potential application for the treatment of ischemic heart diseases. Besides differentiation properties, MSCs protect ischemic cardiomyocytes by secretion of paracrine factors. In this study, we found exosomes enriched with miR-22 were secreted by MSCs following ischemic preconditioning (ExoIPC) and mobilized to cardiomyocytes where they reduced their apoptosis due to ischemia. Interestingly, by time-lapse imaging, we for the first time captured the dynamic shedding of miR-22 loaded exosomes from cytosol to extracellular space. Furthermore, the antiapoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2). In vivo data showed that delivery of ExoIPC significantly reduced cardiac fibrosis. Our data identified a significant benefit of ExoIPC for the treatment of cardiac diseases by targeting Mecp2 via miR-22.

Original languageEnglish (US)
Article numbere88685
JournalPloS one
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 18 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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