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Boosting the Secretion of Mesenchymal Stem/Stromal Cell-Derived Extracellular Vesicles via Metabolic Shift

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Abstract

Mesenchymal stem/stromal cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) have been shown to be promising therapeutic agents in regenerative medicine and tissue engineering due to their high potential capacity for repair in tissue injury, as well as for their neuroprotective, proangiogenic, and immunomodulatory abilities. New evidence suggests that MSC-EVs have greater regenerative and clinical application potential compared to the MSCs themselves, due to advantages of the MSC-EVs’ small size and easy homing. However, one major challenge in MSC-EV clinical application is the relatively low production yield of MSC-EVs. The purpose of this study was to determine if regulating fatty acid oxidation (FAO) could boost EV production yield in MSCs. Results have demonstrated that treatment of MSCs with FAO booster chemical, L-carnitine, robustly increased EV production by around two-fold. In addition, the FAO boosted MSC-EVs did not alter their immunomodulatory function regarding the polarization of macrophages to the anti-inflammatory phenotype. Therefore, FAO booster-mediated MSC-EV yield enhancement is a potential approach to meet the need of producing MSC-EVs in high yield for regenerative medicine applications.

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This item is under embargo until December 9, 2028.