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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