微泡
外体
心肌保护
间充质干细胞
旁分泌信号
细胞生物学
鞘磷脂
生物
再灌注损伤
人口
缺血
生物化学
膜
受体
医学
内科学
小RNA
环境卫生
基因
作者
Ruenn Chai Lai,Fatih Arslan,May May Lee,Siu Kwan Sze,Andre Choo,Tian Sheng Chen,Manuel Salto-Tellez,Leo Timmers,Chuen Neng Lee,Reida El Oakley,Gérard Pasterkamp,Dominique P.V. de Kleijn,Sai Kiang Lim
标识
DOI:10.1016/j.scr.2009.12.003
摘要
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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