Abstract
The therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models. In the current study, we aimed to investigate the effect of extracellular vesicles (EVs) derived from human umbilical cord-MSC (hUCSC-EV) on the clinical score and inflammatory/anti-inflammatory cytokines on the EAE mouse model. After induction of EAE in C57Bl/6 mice, they were treated intravenously with hUCSC-EV or vehicle. The clinical score and body weight of all mice was registered every day. On day 30, mice were sacrificed and splenocytes were isolated for cytokine assay by ELISA. Cytokine expression of pro-/anti-inflammatory cytokine by real-time PCR, leukocyte infiltration by hematoxylin and eosin (H&E) staining, and the percent of glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) positive cells by immunohistochemistry were assessed in the spinal cord. Our results showed that hUCSC-EV-treated mice have lower maximum mean clinical score (MMCS), pro-inflammatory cytokines, and inflammatory score in comparison to the control mice. We also showed that hUCSC-EV administration significantly improved body weight and increased the anti-inflammatory cytokines and the frequency of Treg cells in the spleen. There was no significant difference in the percent of GFAP and MBP positive cells in the spinal cord of experimental groups. Finally, we suggest that intravenous administration of hUCSC-EV alleviate induce-EAE by reducing the pro-inflammatory cytokines, such as IL-17a, TNF-α, and IFN-γ, and increasing the anti-inflammatory cytokines, IL-4 and IL-10, and also decrease the leukocyte infiltration in a model of MS. It seems that EVs from hUC-MSCs have the same therapeutic effects similar to EVs from other sources of MSCs, such as adipose or bone marrow MSCs.
Highlights
The therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models
Jafarinia et al have studied the therapeutic effects of I.V. administration of mesenchymal stem cells (MSCs)-extracellular vesicles (EVs) from human adipose tissue and showed that the maximum mean clinical score and myelin oligodendrocyte glycoprotein (MOG)induced proliferation of splenocytes in MSC-extracellular vesicle (MSC-EV)-treated mice were significantly lower than the control mice; the inflammation score and the percentages of demyelination areas in MSC-EV-treated groups significantly decreased compared with the untreated control group[14]
Our results showed that the maximum mean clinical score (MMCS) of hUCSC-EVs-treated mice was significantly lower than the MMCS of EAE control mice (p < 0.01) (Fig. 3A,B)
Summary
The therapeutic effects of mesenchymal stem cells-extracellular vesicles have been proved in many inflammatory animal models. We suggest that intravenous administration of hUCSC-EV alleviate induce-EAE by reducing the pro-inflammatory cytokines, such as IL-17a, TNF-α, and IFN-γ, and increasing the antiinflammatory cytokines, IL-4 and IL-10, and decrease the leukocyte infiltration in a model of MS It seems that EVs from hUC-MSCs have the same therapeutic effects similar to EVs from other sources of MSCs, such as adipose or bone marrow MSCs. Multiple sclerosis (MS) is a chronic, autoimmune mediated and demyelinating disease of the central nervous system (CNS)[1]. Garcia et al have investigated the effect of I.V. administration of MSC-EVs from human adipose tissue in a progressive model of MS, Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelinating disease Their results showed that I.V. administration of MSC-EVs reduced brain atrophy, decreased inflammatory infiltrates in the spinal cord, improved motor deficits, and increased cell proliferation in the subventricular zone in TMEV infected mice[16]. Based on the above mentioned studies, in the current study, we assessed the effect of EVs derived from human umbilical cord-MSC (hUCSC-EVs) on clinical score and inflammatory/anti-inflammatory cytokines on EAE mouse model
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