CLINICAL RESEARCH · CARDIAC · EXOSOME THERAPY · DREAM BODY CLINIC
Exosome Secreted by MSC Reduces Myocardial Ischemia/Reperfusion Injury
Exosome Secreted by MSC Reduces Myocardial Ischemia/Reperfusion Injury Intro:
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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Key Findings
MSC-secreted exosomes (50–100 nm phospholipid vesicles) are the primary cardioprotective paracrine mechanism following myocardial ischemia/reperfusion injury. Purified exosomes reduced infarct size in a mouse model — demonstrating that cell-free exosome therapy can replicate key cardioprotective effects of MSC therapy.
Exosome Secreted by MSC Reduces Myocardial Ischemia/Reperfusion Injury – Full Study
