Journal of Saveh University of Medical Sciences

The effect of bone marrow mesenchymal stem cell transplantation on Nrf2 deficiency and remyelination in a cuprizone-induced demyelination model

Articles in Press

Document Type : Original Article

Authors

Shirin Barati
fatemeh tahmasebi

Department of Anatomy, Saveh University of Medical Sciences, Saveh, Iran

10.22034/sumsj.2026.579617.1085
Abstract
Introduction: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system accompanied by autoimmune manifestations. Transplanted cells differentiate into various types of neural tissue cells, thereby restoring the functional network and acting as a source of neurotrophic factors to support the remaining cells in the tissue. This study emphasis’s the importance of oligodendrocytes in inhibiting or reducing demyelination in an experimental MS model and investigates the effect of transplanted bone marrow mesenchymal stem cells on oligodendrocyte lineages by examining the Nrf2 mechanism.
Methods: This study used 8-week-old male C57BL/6 mice. To induce the chronic demyelination model of MS, the mice received a diet containing 0.2% cuprizone per kilogram of food for 12 weeks. Bone marrow-derived mesenchymal stem cell transplants were then injected into the right lateral ventricle of the mice via intraventricular injection. The rotarod behavioral test was used to assess behavioral impairment and recovery rate. Two weeks after cell injection, the rate of remyelination and axon repair was studied using Luxol Fast Blue (LFB) staining. The expression levels of the CX3CL1, TGF-β and Nrf2 genes were evaluated using real-time PCR. Finally, statistical analyses were performed using SPSS software and a t-test and one-way ANOVA. Mean ± SEM was used to describe the data and P < 0.05 was considered significant.
Results: In this study, we found that, compared to other groups, mesenchymal stem cell transplantation increased the expression of the TGF-β, CX3CL1 and Nrf2 genes, as well as improving function. Furthermore, cell transplantation was found to significantly improve myelination and axonal repair, as assessed by LFB images.
Conclusion: The findings of this study finally showed that the intraventricular injection of mesenchymal stem cells can be an effective treatment for chronic demyelination in neurodegenerative diseases such as MS. This is because, on the one hand, cell therapy reduces oxidative stress and inflammation by using factors secreted by cells in the culture medium and, on the other hand, it increases the rate of myelination and axonal repair. Therefore, cell transplantation can be considered a suitable method for enhancing myelination and reducing inflammation in diseases such as MS.

Keywords

Stem cell
cuprizone model
Nrf2
MS
Journal of Saveh University of Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 13 May 2026

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