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oai:repisalud.isciii.es:20.500.12105/99572024-09-27T09:25:38Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Alvarez, Veronica author Sánchez-Margallo, Francisco Miguel author Macías-García, Beatriz author Gomez-Serrano, Maria author Jorge, Inmaculada author Vazquez, Jesus author Blázquez, Rebeca author Casado, Javier G author 2018-10 Endometrial mesenchymal stem cells (endMSCs) reside in the basal and functional layer of human endometrium and participate in tissue remodelling, which is required for maintaining the regenerative capacity of the endometrium. The endMSCs are multipotent stem cells and exhibit immunomodulatory effects. This paper aimed to evaluate the regulatory effects of extracellular vesicles derived from endMSCs (EV-endMSCs) in the setting of T cell activation. In vitro stimulations of lymphocytes were performed in the presence of EV-endMSCs. These in vitro-stimulated lymphocytes were functionally and phenotypically characterized to distinguish CD4+ and CD8+ T cell differentiation subsets. Moreover, the inhibition of TGFβ was performed with neutralizing antibodies. The phenotype and nanoparticle tracking analysis of the EV-endMSCs demonstrated that they are similar in terms of size distribution to other mesenchymal stem cells-derived exosomes. The in vitro assays showed an immunomodulatory potential of these vesicles to counteract the differentiation of CD4+ T cells. The quantification of active TGFβ in EV-endMSCs was found to be very high when compared with extracellular vesicles-free concentrated supernatants. Finally, the neutralization of TGFβ significantly attenuated the immunomodulatory activity of EV-endMSCs. In summary, this is the first report demonstrating that EV-endMSCs exhibit a potent inhibitory effect against CD4+ T cell activation, which is partially mediated by TGFβ signalling. Wiley 10.1002/term.2743 1932-7005 1932-6254 Journal of tissue engineering and regenerative medicine 30058282 http://hdl.handle.net/20.500.12105/9957 TGFβ Endometrial mesenchymal stem cells Extracellular vesicles Immunomodulation Lymphocyte activation Lymphocyte differentiation The immunomodulatory activity of extracellular vesicles derived from endometrial mesenchymal stem cells on CD4+ T cells is partially mediated by TGFbeta