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Stem Cells International
Volume 2015, Article ID 659890, 14 pages
http://dx.doi.org/10.1155/2015/659890
Research Article

Exosomes Secreted from CXCR4 Overexpressing Mesenchymal Stem Cells Promote Cardioprotection via Akt Signaling Pathway following Myocardial Infarction

1Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA
2Department of Cardiology, The People’s Hospital of Sanya, Sanya, Hainan 572000, China
3Department of Urinary Surgery, Xining City Hospital, Qinghai 810000, China
4Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267, USA
5Infection Hospital of Nanchang University, Nanchang, Jiangxi 330002, China

Received 4 December 2014; Revised 16 January 2015; Accepted 21 January 2015

Academic Editor: Daniele Avitabile

Copyright © 2015 Kai Kang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Objective. Exosomes secreted from mesenchymal stem cells (MSC) have demonstrated cardioprotective effects. This study examined the role of exosomes derived from MSC overexpressing CXCR4 for recovery of cardiac functions after myocardial infarction (MI). Methods. In vitro, exosomes from MSC transduced with lentiviral CXCR4 (ExoCR4) encoding a silencing sequence or null vector were isolated and characterized by transmission electron microscopy and dynamic light scattering. Gene expression was then analyzed by qPCR and Western blotting. Cytoprotective effects on cardiomyocytes were evaluated and effects of exosomes on angiogenesis analyzed. In vivo, an exosome-pretreated MSC-sheet was implanted into a region of scarred myocardium in a rat MI model. Angiogenesis, infarct size, and cardiac functions were then analyzed. Results. In vitro, ExoCR4 significantly upregulated IGF-1α and pAkt levels and downregulated active caspase 3 level in cardiomyocytes. ExoCR4 also enhanced VEGF expression and vessel formation. However, effects of ExoCR4 were abolished by an Akt inhibitor or CXCR4 knockdown. In vivo, ExoCR4 treated MSC-sheet implantation promoted cardiac functional restoration by increasing angiogenesis, reducing infarct size, and improving cardiac remodeling. Conclusions. This study reveals a novel role of exosomes derived from MSCCR4 and highlights a new mechanism of intercellular mediation of stem cells for MI treatment.