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Mesenchymal stem cells (MSCs) have been approved as a cellular drug for the treatment of a variety of immune-related diseases by the government of many countries'. Previous investigations, including ours, have shown that exosomes secreted by MSCs (MSC-ex) are one of the main factors responsible for the therapeutic effect of MSCs. However, the immune modulation activities and the contents of MSC-ex derived from cells under different incubation conditions differ dramatically. Therefore, the optimal way to ensure effectiveness is by identifying and preparing MSC-ex with confirmed potent immunosuppressive activity. The aim of this study was to investigate and analyze the composition and function of MSC-ex secreted by MSCs stimulated by different cytokines to obtain exosomes with more potent immunosuppressive activity. To achieve this aim, umbilical cord-derived MSCs were treated with PBS, TGF-β, IFN-γ, or TGF-β plus IFN-γ for 72 hr. Then, exosomes were isolated from the culture supernatants. Common exosome markers, such as CD9, CD63, and CD81, were detected and analyzed by FCM. At the same time, the TGF-β, IFN-γ, IDO, and IL-10 content in exosomes was detected, and the influence of exosmes from defferent groups on the induction of mononuclear cell transformation into Tregs was analyzed via FCM. Our results show that the TGF-β combined with IFN-γ exosome group more effectively promoted the transformation of mononuclear cells to Tregs, and the analysis showed that IDO may play an important role. This study might provide a novel strategy to treat GVHD as well as other immune-associated disorders. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate the therapeutic effect of Mesenchymal stem cell-derived exosomes (MSC-exs) on eczema mice model. Eczema mice were established by 2, 4-two nitrochlorobenzene. Human umbilical cords cells and exosomes were harvested. In eczema mice model, the effect of MSC-ex on eczema was evaluated by severity score, atopic dermatitis score and histopathological analysis of dermis. MTT tests were performed to assess PBMC proliferation. Treg was identified by flow cytometry. The angiogenesis was analyzed by endothelial cell tube formation assay. Compared with PBS, the wound closure of animals treated with MSC-exs was faster. After MSC-exs treatment, there were more new epidermis and dermis, and less scar formation of the lesion. There were significant differences in the integral score of skin injury and the number of lymphocyte infiltration in the skin between the treatment group and the PBS group (p <.01). MSC-exs significantly inhibit Peripheral blood mononuclear cell proliferation, promote the transformation of Treg and the formation of endothelial tube. MSC-ex accelerated wounds healing in mice eczema model by inhibiting inflammatory cell infiltration and promoting vascular formation. [ABSTRACT FROM AUTHOR]