Thermally engineered MSC-derived extracellular vesicles ameliorate colitis in mice by restoring the imbalanced
Deqian Tang1, Manqing Liu1, Shenghan Gao2
1Hospital of Stomatology, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou 510055, China; Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, China.
Abstract:
Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have garnered extensive interest for their immunomodulatory properties in immune-mediated inflammatory diseases. However, the development of EVs as clinical drugs often faces challenges such as low production yield and suboptimal therapeutic efficacy. In this study, we discovered that thermally engineering was able to enhance the yield of MSC-EVs. Moreover, the PD-L1 expression of EVs released from the thermal engineering MSCs was found to be upregulated significantly, and these EVs ameliorated the symptoms and pathological damages in murine dextran sulfate sodium (DSS)-induced colitis model. The therapeutic effect on DSS-induced colitis was mediated through the regulation of the Th17/Treg cell balance, demonstrating the immunomodulatory properties of the thermally engineering MSC-EVs. Overall, our findings suggest that thermal engineering can be utilized as a promising strategy for enhancing EV production and may provide a potential therapeutic approach for clinical treatment of colitis.


