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Surgical Porcine Model of Chronic Myocardial Ischemia Treated by Exosome-laden Collagen Patch and Off-pump Coronary Artery Bypass Graft
Published on: September 15, 2023
Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury
Ruenn Chai Lai1, Fatih Arslan, May May Lee
1Institute of Medical Biology, ASTAR, 138648 Singapore.
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.
Insights
Mesenchymal stem cells secrete exosomes, which are tiny particles that protect the heart from injury. These exosomes represent a new therapeutic approach for tissue repair and treating heart damage.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Cell Biology
Background:
- Mesenchymal stem cells (MSCs) secrete factors that protect the heart from ischemia/reperfusion injury.
- This cardioprotective effect was previously attributed to large extracellular complexes.
Purpose of the Study:
- To investigate the nature of the cardioprotective factors secreted by MSCs.
- To determine if these factors are exosomes and if they mediate cardioprotection.
Main Methods:
- Characterization of 50-100 nm particles secreted by MSCs using electron microscopy.
- Analysis of particle composition (phospholipids, exosome markers like CD81, CD9, Alix).
- Purification of particles via HPLC and assessment of their effect on infarct size in a mouse model of myocardial ischemia/reperfusion injury.
Main Results:
- MSCs secrete 50-100 nm phospholipid vesicles identified as exosomes.
- These purified exosomes contain exosome-associated proteins.
- Administered exosomes significantly reduced infarct size in a mouse model of heart injury.
Conclusions:
- MSC-mediated cardioprotection during myocardial ischemia/reperfusion injury is primarily mediated by secreted exosomes.
- This finding reveals a novel mechanism for intercellular communication in tissue repair.
- MSC-derived exosomes offer a promising avenue for developing new biologics for tissue regeneration and therapeutic applications.
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