Faculty of Veterinary Medicine, Urmia University Veterinary Research Forum 2008-8140 3 4 2012 12 01 Phenotypic modulation of auto-reactive cells by insertion of tolerogenic molecules via MSC-derived exosomes 257 261 1599 EN Aram Mokarizadeh Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Nowruz Delirezh Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Ahhmad Morshedi Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran Ghasem Mosayebi Department of Immunology and Microbiology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran Bahram Dalir-Naghadeh Department of Clinical Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran 0000-0002-2319-6697 Journal Article 2012 12 28 Auto-reactive cells-mediated immune responses are responsible for the current tissue damages during autoimmunity. Accordingly, functional modulation of auto-reactive cells has been a pivotal aim in many of recent studies. In the current study, we investigated the possibility for insertion of regulatory molecules onto auto-reactive cells through exosomal nano-shuttles as a novel approach for phenotype modification of auto-reactive cells. The exosomes were isolated from supernatant of mesenchymal stem cells culture. Resultant exosomes co-cultured with lymphocytes were harvested from established EAE mice in the presence of antigenic MOG35-55 peptide. After 24 hr, insertion of exosomal tolerogenic molecules (PD-L1, TGF-β, galectin-1) onto auto-reactive cells were explored through flow cytometry. The potency of exosomal inserted membrane molecules to modulate phenotype of auto-reactive lymphocytes was assessed upon ELISA test for their-derived cytokines IFN-γ and IL-17. Incorporation of exosomal molecules into lymohocytes’ membrane was confirmed by flow cytometric analyses for surface levels of mentioned molecules. Additionally, the decreased secretion of IFN-γ and IL-17 were detected in exosome pre-treated lymphocytes upon stimulation with MOG peptide. Mesenchymal stem cells -derived exosomes showed to be efficient organelles for insertion of bioactive tolerogenic molecules onto auto-reactive cells and modulation of their phenotypes. https://vrf.iranjournals.ir/article_1599_83e8ef518174e1eb6be4a0778d050c9d.pdf