Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury

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 visualize...

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Bibliographic Details
Published in:Stem cell research 2010-05, Vol.4 (3), p.214-222
Main Authors: Lai, Ruenn Chai, Arslan, Fatih, Lee, May May, Sze, Newman Siu Kwan, Choo, Andre, Chen, Tian Sheng, Salto-Tellez, Manuel, Timmers, Leo, Lee, Chuen Neng, El Oakley, Reida Menshawe, Pasterkamp, Gerard, de Kleijn, Dominique P.V., Lim, Sai Kiang
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - metabolism
Calcium-Binding Proteins - metabolism
Cardiotonic Agents - therapeutic use
Chromatography, High Pressure Liquid
Disease Models, Animal
Exosomes - metabolism
Exosomes - physiology
Humans
Membrane Glycoproteins - metabolism
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Mice
Microscopy, Electron
Myocardial Ischemia - therapy
Reperfusion Injury - therapy
Tetraspanin 28
Tetraspanin-29
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Summary: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.
ISSN:1873-5061
1876-7753
DOI:10.1016/j.scr.2009.12.003