title: Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22.
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 (Exo(IPC)) 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 anti-apoptotic effect of miR-22 was mediated by direct targeting of methyl CpG binding protein 2 (Mecp2). In vivo data showed that delivery of Exo(IPC) significantly reduced cardiac fibrosis. Our data identified a significant benefit of Exo(IPC) for the treatment of cardiac diseases by targeting Mecp2 via miR-22.
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Cardiovascular Institute, Southern Medical University, Guangzhou, China ; Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Mashhood
authors.initials: M
authors.lastname: Wani
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangdong Provincial Cardiovascular Institute, Southern Medical University, Guangzhou, China.
authors.forename: Xiyong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
mesh_terms: D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D018920:Coculture Techniques; D055354:Exosomes / Q000378:metabolism*; D005355:Fibrosis; D019194:Ischemic Preconditioning; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D057054:Molecular Imaging; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D032383:Myocytes, Cardiac / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D051783:Methyl-CpG-Binding Protein 2; D035683:MicroRNAs; C574876:Mirn22 microRNA, mouse