Ischemic Preconditioning Potentiates the Protective Effect of Stem Cells through Secretion of Exosomes by Targeting Mecp2 via miR-22

• Published in: PloS one Vol. 9; no. 2; p. e88685
• Main Authors: Feng, Yuliang, Huang, Wei, Wani, Mashhood, Yu, Xiyong, Ashraf, Muhammad
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.02.2014; Public Library of Science (PLoS)
• Subjects: Animals; Apoptosis; Base Sequence; Biology; Bone marrow; Cardiomyocytes; Cardiovascular diseases; Cell culture; Cell Survival; Coculture Techniques; Coronary artery disease; Cytosol; Data processing; Exosomes; Exosomes - metabolism; Fibrosis; Heart; Heart diseases; Ischemia; Ischemic Preconditioning; Laboratory animals; MeCP2 protein; Medical research; Medical treatment; Medicine; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchyme; Methyl-CpG binding protein; Methyl-CpG-Binding Protein 2 - genetics; Mice; MicroRNAs; MicroRNAs - genetics; Molecular Imaging; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocytes, Cardiac - pathology; Oligonucleotide Array Sequence Analysis; Paracrine signalling; Pathology; Preconditioning; Protein binding; Secretion; Shedding; Stem cells; United States > US; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0088685

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.