Elsevier

Stem Cell Research

Volume 4, Issue 3, May 2010, Pages 214-222
Stem Cell Research

Regular article
Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury

https://doi.org/10.1016/j.scr.2009.12.003Get rights and content
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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.

Abbreviations

AMI
acute myocardial Infarction
CM
conditioned medium
MI/R
myocardial ischemia/reperfusion
MSCs
mesenchymal stem cells
MWCO
molecular weight cut off
NCM
nonconditioned medium

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