biostudies-literatureDing YNational Natural Science Grant of ChinaNatural Science Foundation of ShanghaiPyramid Talent Projectszaf009https://www.ebi.ac.uk/biostudies/studies/S-EPMC12012893biostudies-literatureUnknown14(4)<h4>Background</h4>Mesenchymal stem cells (MSCs) require priming by proinflammatory stimuli for optimal immunosuppressive effects. Our previous work identified mixed lymphocyte reaction-conditioned medium (MLR-CdM) as a potent enhancer of MSC immunosuppressive properties. This study evaluates the immunomodulatory potential of MSC-derived extracellular vesicles preconditioned with MLR-CdM (MSC-EVMLR) compared to IFN-γ (MSC-EVIFN), focusing on key miRNAs and mechanisms involved.<h4>Methods</h4>We assessed the ability of MSC-EVMLR and MSC-EVIFN to modulate lymphocyte proliferation and cytokine expression in vitro. To identify potential effector molecules within MSC-EVMLR, we performed miRNA array analysis combined with dose-response experiments using MLR-CdM under varying stimulation conditioStem cells translational medicineMixed lymphocyte reaction-conditioned MSC-derived extracellular vesicles enhance graft survival via miR-638-mediated immunoregulation.PMC1201289381500207YQ67724ZR1459300Ding YZheng XLiang XLin FZhu FChen YMa KHan SWang JfalseMixed lymphocyte reaction-conditioned MSC-derived extracellular vesicles enhance graft survival via miR-638-mediated immunoregulation.<h4>Background</h4>Mesenchymal stem cells (MSCs) require priming by proinflammatory stimuli for optimal immunosuppressive effects. Our previous work identified mixed lymphocyte reaction-conditioned medium (MLR-CdM) as a potent enhancer of MSC immunosuppressive properties. This study evaluates the immunomodulatory potential of MSC-derived extracellular vesicles preconditioned with MLR-CdM (MSC-EVMLR) compared to IFN-γ (MSC-EVIFN), focusing on key miRNAs and mechanisms involved.<h4>Methods</h4>We assessed the ability of MSC-EVMLR and MSC-EVIFN to modulate lymphocyte proliferation and cytokine expression in vitro. To identify potential effector molecules within MSC-EVMLR, we performed miRNA array analysis combined with dose-response experiments using MLR-CdM under varying stimulation conditio2025-01-01T00:00:00Z2025 Apr2025-07-01T03:05:19.33Z2025-07-01T03:05:19.33ZS-EPMC120128934026120010.1093/stcltm/szaf009