| 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. | |
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MedLine Citation:
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PMID: 23399448 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2013-1-14 |
Journal Detail:
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Title: Stem cell research Volume: 10 ISSN: 1876-7753 ISO Abbreviation: Stem Cell Res Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-2-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101316957 Medline TA: Stem Cell Res Country: - |
Other Details:
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Languages: ENG Pagination: 301-312 Citation Subset: - |
Copyright Information:
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Copyright © 2013 Elsevier B.V. All rights reserved. |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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