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
Institute of Medical Biology, ASTAR, 138648 Singapore.
Stem Cell Res. 2010 May;4(3):214-22. doi: 10.1016/j.scr.2009.12.003. Epub 2010 Jan 4.
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.
人胚胎干细胞来源的间充质干细胞（MSC）条件培养基（CM）先前已被证明可通过50 - 100纳米的大复合物在心肌缺血/再灌注损伤期间介导心脏保护作用。在此我们表明，这些间充质干细胞分泌50至100纳米的颗粒。这些颗粒可通过电子显微镜观察到，并且显示为由胆固醇、鞘磷脂和磷脂酰胆碱组成的磷脂囊泡。它们含有共免疫沉淀的外泌体相关蛋白，例如CD81、CD9和Alix。通过在高效液相色谱上进行尺寸排阻分级分离，这些颗粒被纯化成为水动力半径为55 - 65纳米的均匀颗粒群体。这些观察结果共同表明这些颗粒是外泌体。这些纯化的外泌体在心肌缺血/再灌注损伤的小鼠模型中减小了梗死面积。因此，间充质干细胞通过分泌外泌体介导其心脏保护旁分泌效应。外泌体的这一新作用为组织损伤和修复的细胞间介导提供了新的视角，并为组织修复生物制品的开发带来了新方法。
