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Updated: Nov 26, 2025
Systemic Injection of Neural Stem/Progenitor Cells in Mice with Chronic EAE
Published on: April 15, 2014
Intranasal administration of small extracellular vesicles derived from mesenchymal stem cells ameliorated the
Anwar Fathollahi1, Seyed Mahmoud Hashemi1, Mostafa Haji Molla Hoseini1
1Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:
Experimental autoimmune encephalomyelitis (EAE) is a mouse model for the human multiple sclerosis, which is characterized by inflammation in the central nervous system (CNS), de-myelination of axonal neurons, and loss of motor coordination. The aim of the current study was to evaluate the effect of intranasal administration of mesenchymal stem cells (MSCs) and small extracellular vesicle (SEV) derived from the MSC (MSC-SEV) on disease activity and antigen-specific responses in the EAE mouse model. MSCs (5 × 105) were administered intranasally to EAE mice (n = 5) on the 15th and 24th days after immunization. In addition, the intranasal administration of MSC-SEV (10 μg) was used to treat EAE mice (n = 5) on a daily basis from the 15th to the 27th day after induction of the disease. The outcomes of therapies were evaluated using studying clinical symptoms and histological analysis of CNS lesions. Moreover, T cell proliferation, the frequency of regulatory T cells, the expression of transcription factors of T-helper subsets, and the levels of their corresponded cytokines were evaluated in splenocytes culture that was stimulated with specific-antigen. The results of treatment of EAE mice with MSC- SEV and MSC showed a significant decrease in the clinical scores, and it was found that treatment with MSC-SEV was more effective in alleviating clinical scores than MSC. In addition, the decrease in clinical symptoms was associated with an increase in immunomodulatory responses, including an increase in the frequency of Foxp3+ CD25+ regulatory T cells. Moreover, the level of TGF-β was increased by both treatments; however, interleukin-10 was increased only by MSC treatment. Ultimately, it was achieved that the intranasal administration of MSC-SEV to EAE mice was more effective than the administration of MSC to reduce clinical scores and histological lesions of the CNS tissue.
Insights
Intranasal mesenchymal stem cell-derived small extracellular vesicles (MSC-SEVs) more effectively treat experimental autoimmune encephalomyelitis (EAE) in mice than MSCs. MSC-SEVs reduced clinical scores and CNS lesions by enhancing immunomodulatory responses.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Experimental autoimmune encephalomyelitis (EAE) is a key mouse model for human multiple sclerosis.
- EAE is characterized by CNS inflammation, demyelination, and motor coordination loss.
Purpose of the Study:
- To evaluate the efficacy of intranasal mesenchymal stem cells (MSCs) and MSC-derived small extracellular vesicles (MSC-SEVs) in an EAE mouse model.
- To assess the impact of these treatments on disease activity and antigen-specific immune responses.
Main Methods:
- EAE mice received intranasal MSCs or MSC-SEVs at specific time points post-immunization.
- Clinical symptoms and central nervous system (CNS) histological lesions were analyzed.
- Splenocytes were assessed for T cell proliferation, regulatory T cell frequency, T-helper subset transcription factors, and cytokine levels.
Main Results:
- Both MSCs and MSC-SEVs significantly reduced clinical scores and CNS lesions in EAE mice.
- MSC-SEV treatment demonstrated superior efficacy in alleviating clinical symptoms compared to MSC treatment.
- Treatments increased the frequency of regulatory T cells (Foxp3+ CD25+) and TGF-β levels; MSCs uniquely increased IL-10.
Conclusions:
- Intranasal MSC-SEV administration is a more effective therapeutic strategy than MSCs for reducing EAE clinical scores and CNS pathology.
- MSC-SEVs promote immunomodulatory responses, offering a promising therapeutic avenue for multiple sclerosis.
