Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury

• Published in: Stem cell research Vol. 4; no. 3; pp. 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: Journal Article
• Language: English
• Published: England Elsevier B.V 01.05.2010
• 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; NCM; MSCs; MWCO; CM; MI/R; AMI
• ISSN: 1873-5061; 1876-7753
• DOI: 10.1016/j.scr.2009.12.003

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.