Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury |
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Authors: | Ruenn Chai Lai Fatih Arslan May May Lee Newman Siu Kwan Sze Andre Choo Tian Sheng Chen Manuel Salto-Tellez Leo Timmers Chuen Neng Lee Reida Menshawe El Oakley Gerard Pasterkamp Dominique PV de Kleijn Sai Kiang Lim |
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Institution: | 1. Institute of Medical Biology, A?STAR, 8A Biomedical Grove, 138648 Singapore;2. National University of Singapore (NUS), Graduate School for Integrative Sciences and Engineering, 28 Medical Drive, 117456 Singapore;3. Laboratory of Experimental Cardiology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands;4. Bioprocessing Technology Institute, A?STAR, 20 Biopolis Way, 138671 Singapore;5. School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore;6. Division of Bioengineering, Faculty of Engineering, NUS, 7 Engineering Drive 1, 117574 Singapore;7. Department of Pathology, YLL School of Medicine, NUS, 5 Lower Kent Ridge Road, 119074 Singapore;8. Department of Surgery, YLL School of Medicine, NUS, 5 Lower Kent Ridge Road, 119074 Singapore;9. Interuniversity Cardiology Institute of the Netherlands, Catharijnesingel 52, 3511 GC Utrecht, The Netherlands |
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Abstract: | Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50–100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine. They contained coimmunoprecipitating exosome-associated proteins, e.g., CD81, CD9, and Alix. These particles were purified as a homogeneous population of particles with a hydrodynamic radius of 55–65 nm by size-exclusion fractionation on a HPLC. Together these observations indicated that these particles are exosomes. These purified exosomes reduced infarct size in a mouse model of myocardial ischemia/reperfusion injury. Therefore, MSC mediated its cardioprotective paracrine effect by secreting exosomes. This novel role of exosomes highlights a new perspective into intercellular mediation of tissue injury and repair, and engenders novel approaches to the development of biologics for tissue repair. |
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