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Evaluation of in vivo lithium chloride effects as a GSK3-β inhibitor on human adipose derived stem cells differentiation into oligodendrocytes and re-myelination in an animal model of multiple sclerosis

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Abstract

Background

The application of neuroprotective agents in combination with stem cells is considered a potential effective treatment for multiple sclerosis (MS). Therefore, the effects of lithium chloride as a neuroprotective agent and a GSK3-β inhibitor were evaluated in combination with human adipose derived stem cells on re-myelination, oligodendrocyte differentiation, and functional recovery.

Methods

After inducing a mouse model of MS and proving it by the hanging wire test, the mice were randomly assigned to five experimental groups: Cup, Sham, Li, hADSC, and Li + hADSC. Additionally, a control group with normal feeding was considered. Finally, toluidine blue staining was carried out to estimate the level of myelination. Furthermore, immunofluorescent staining was used to evaluate the mean of OLIG2 and MOG positive cells. The mRNA levels of β-Catenin, myelin and oligodendrocyte specific genes were determined via the Real-Time PCR.

Results

The results of the hanging wire test and toluidine blue staining showed a significant increase in myelin density and improvements in motor function in groups, which received lithium and stem cells, particularly in the Li + hADSC group compared with the untreated groups (P < 0.01). Moreover, immunostaining results indicated that the mean percentages of MOG and OLIG2 positive cells were significantly higher in the Li + hADSC group than in the other groups (P < 0.01). Finally, gene expression studies indicated that the use of lithium could increase the expression of β-Catenin, myelin and oligodendrocyte specific genes.

Conclusion

The use of Lithium Chloride can increase stem cells differentiation into oligodendrocytes and improve re-myelination in MS.

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Data availability

Data are available from the corresponding authors upon reasonable request.

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Acknowledgements

This study was conducted as a part of the Ph.D. thesis, and we acknowledge Isfahan University of Medical Sciences for providing the facilities and support. It should be noted that this article was previously published online as a preprint manuscript (DOI: https://doi.org/10.21203/rs.3.rs-2083375/v1). License: This work is licensed under a Creative Commons Attribution 4.0 International License.

Funding

This work was supported by Isfahan University of Medical Sciences (Grant Number: 399831).

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Authors and Affiliations

  1. Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

    Sahar Ghosouri, Mitra Soleimani, Mohammad Bakhtiari & Nazem Ghasemi

Authors
  1. Sahar Ghosouri
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  2. Mitra Soleimani
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  3. Mohammad Bakhtiari
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  4. Nazem Ghasemi
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Contributions

SG and NG: participated in the conception, design, statistical analysis, and drafting of the manuscript. SG and MB: contributed to data collection and manuscript drafting. MS: revised the manuscript.

Corresponding author

Correspondence to Nazem Ghasemi.

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There is no conflict of interest.

Ethical approval

This experimental study was conducted on the female C57BL/6 mice model of MS at the Central Laboratory of Isfahan University of Medical Sciences. Meanwhile, all procedures of research were conducted according to the guidelines of the Iranian Committee of Animal care approved by the Ethics Committee (Ethics#IR.MUI.MED.REC.1399.925).

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Ghosouri, S., Soleimani, M., Bakhtiari, M. et al. Evaluation of in vivo lithium chloride effects as a GSK3-β inhibitor on human adipose derived stem cells differentiation into oligodendrocytes and re-myelination in an animal model of multiple sclerosis. Mol Biol Rep 50, 1617–1625 (2023). https://doi.org/10.1007/s11033-022-08181-8

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  • DOI: https://doi.org/10.1007/s11033-022-08181-8

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