Document Detail


Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury.
MedLine Citation:
PMID:  23399448     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We have previously identified exosomes as the paracrine factor secreted by mesenchymal stem cells. Recently, we found that the key features of reperfusion injury, namely loss of ATP/NADH, increased oxidative stress and cell death were underpinned by proteomic deficiencies in ischemic/reperfused myocardium, and could be ameliorated by proteins in exosomes. To test this hypothesis in vivo, mice (C57Bl6/J) underwent 30min ischemia, followed by reperfusion (I/R injury). Purified exosomes or saline was administered 5min before reperfusion. Exosomes reduced infarct size by 45% compared to saline treatment. Langendorff experiments revealed that intact but not lysed exosomes enhanced viability of the ischemic/reperfused myocardium. Exosome treated animals exhibited significant preservation of left ventricular geometry and contractile performance during 28days follow-up. Within an hour after reperfusion, exosome treatment increased levels of ATP and NADH, decreased oxidative stress, increased phosphorylated-Akt and phosphorylated-GSK-3β, and reduced phosphorylated-c-JNK in ischemic/reperfused hearts. Subsequently, both local and systemic inflammation were significantly reduced 24h after reperfusion. In conclusion, our study shows that intact exosomes restore bioenergetics, reduce oxidative stress and activate pro-survival signaling, thereby enhancing cardiac function and geometry after myocardial I/R injury. Hence, mesenchymal stem cell-derived exosomes are a potential adjuvant to reperfusion therapy for myocardial infarction.
Authors:
Fatih Arslan; Ruenn Chai Lai; Mirjam B Smeets; Lars Akeroyd; Andre Choo; Eissa N E Aguor; Leo Timmers; Harold V van Rijen; Pieter A Doevendans; Gerard Pasterkamp; Sai Kiang Lim; Dominique P de Kleijn
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-14
Journal Detail:
Title:  Stem cell research     Volume:  10     ISSN:  1876-7753     ISO Abbreviation:  Stem Cell Res     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-2-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101316957     Medline TA:  Stem Cell Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  301-312     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Elsevier B.V. All rights reserved.
Affiliation:
Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; The Netherlands Heart Institute (ICIN), Utrecht, the Netherlands; Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands. Electronic address: f.arslan@umcutrecht.nl.
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