Since in cell therapy, there are always concerns about immune rejection, genetic disability, and malignancies, special attention has been paid to extracellular vesicles (EVs) which are secreted by mesenchymal stem cells (MSCs). In the present study, we assessed and compared the therapeutic effects of human adipose-derived mesenchymal stem cells (hADSC) and hADSC-EVs from adipose tissue on experimental autoimmune encephalomyelitis (EAE). After induction of EAE in C57Bl/6 mice, they were treated with hADSCs, hADSC-EVs, or vehicle intravenously. The clinical score of all mice was recorded every other day. Mice were killed at Day 30 and splenocytes were isolated for proliferation assay and determination of the frequency of Treg cells by flow cytometry. Leukocyte infiltration by hematoxylin and eosin, percentages of demyelination areas by luxol fast blue, and mean fluorescence intensity of oligodendrocyte transcription factor 2 (OLIG2) and myelin basic protein (MBP) by immunohistochemistry were assessed in the spinal cord. Our results showed that the maximum mean clinical score and myelin oligodendrocyte glycoprotein-induced proliferation of splenocytes in hADSC- and hADSC-EV-treated mice were significantly lower than the control mice (p < .05). We also demonstrated that the frequency of CD4+ CD25+ Foxp3+ cells was significantly higher in the spleen of hADSC-treated mice than EAE control mice (p = .023). The inflammation score and the percentages of demyelination areas in hADSC- and hADSC-EV-treated groups significantly declined compared with the untreated control group (p < .05). We also showed that there was no significant difference in MFI of MBP and OLIG2 in the spinal cord of studied groups. Overall, we suggest that intravenous administration of hADSC-EVs attenuates the induced EAE through diminishing proliferative potency of T cells, mean clinical score, leukocyte infiltration, and demyelination in a chronic model of multiple sclerosis.
Keywords: adipose tissue; experimental autoimmune encephalomyelitis; extracellular vesicles; human adipose-derive mesenchymal stem cells; mesenchymal stem cells; multiple sclerosis.
© 2020 Wiley Periodicals, Inc.