exosomes from adipose tissue-derived mesenchymal stem cells induce regulatory t cells in covid-19 patients

An imbalance between regulatory t (treg) and t-helper (th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (covid-19). mesenchymal stem cells (mscs) exert immunomodulatory properties through secreting exosomes. this study aimed to assess the effect of msc-derived exosomes (msc-exo) on the differentiation of peripheral blood mononuclear cells (pbmcs) into tregs from patients with covid-19. exosomes were isolated from adipose tissue-derived mscs. pbmcs were separated from the whole blood of covid-19 patients (n=20). treg frequency was assessed before and 48 hours after treatment of pbmcs with msc-exo using flow cytometry. expression of foxp3 and cytokine genes, and the concentration of cytokines associated with tregs, were assessed before and after treatment with msc-exo. the frequency of cd4^+cd25^+cd127ˉ tregs was significantly higher after treating pbmcs with msc-exo (6.695±2.528) compared to before treatment (4.981±2.068). the expressions of transforming growth factor (tgf)-β1, interleukin (il)-10, and foxp3 were significantly upregulated in msc-exo–treated pbmcs. the concentration of il‐10 increased significantly after treatment (994.7±543.9 pg/ml) of pbmcs with msc-exo compared with before treatment (563.5±408.6 pg/ml). the concentration of tgf-β was significantly higher in the supernatant of pbmcs after treatment with msc-exo (477.0±391.1 pg/ml) than pbmcs before treatment (257.7±226.3 pg/ml). msc-exo has the potential to raise anti-inflammatory responses by induction of tregs, potentiating its therapeutic effects in covid-19.