Protective activity of adipose-derived stem cell extracellular vesicles in ischemia and/or reperfusion

Abstract

Increasing evidence of the significant clinical value of protection against ischemia/reperfusion injury has contributed to the realization of the independent importance of this approach in improving prognosis and reducing cardiovascular mortality. Extracellular vesicles (EVs) derived by adipose mesenchymal stem cells may mediate the paracrine effects of stem cells and provide regenerative and anti-inflammatory properties, which are enhanced by γ-aminobutyric acid. The protective effects on cardiac myocytes may result from the EV embarked by miR-21-5p, which is a target for thioredoxin-interacting protein, regulating the formation of thioredoxin-interacting protein-thioredoxin complexes and subsequently enhancing the antioxidant activity of thioredoxin. It has been found that γ-aminobutyric acid governs myocardial bioenergetics through suppressing inflammation and supporting mitochondrial structure. Finally, stem cell-based cell-free therapy based on adipose-derived stem cell EVs is considered a promising approach to individualized management of ischemia-induced cardiomyopathy.

Keywords: Extracellular vesicles; Adipose mesenchymal stem cells; MicroRNA-21-5p; Cardiac protection; Ischemia; Reperfusion

Core Tip: Extracellular vesicles, which are specifically derived from immunoregulatory cells such as mesenchymal stem cells or cardiac progenitor cells, have been shown to be important mediators of intercellular communication. They are ideally suited for cell-free regenerative cardiac therapy due to their low immunogenicity and high level of active molecule delivery safety. Extracellular vesicles derived from adipose-derived mesenchymal stem cell seem to show cardiac protective effects through their ability to deliver miR-21-5p acting via thioredoxin-interacting protein-thioredoxin complexes and subsequently to mediate anti-ischemic and antioxidant effects in ischemia and/or reperfusion injury.