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Bone marrow mesenchymal stem cells to ameliorate experimental autoimmune encephalomyelitis via modifying expression patterns of miRNAs

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Abstract

Introduction

Clinical and experimental studies highlighted the significant therapeutic role of Mesenchymal stem cells (MSCs) in neurodegenerative diseases. MSCs possess potent immunomodulatory properties by releasing exosomes, which generate a suitable microenvironment. microRNAs (miRNAs), as one of several effective bioactive molecules of exosomes, influence cellular communication and activities in recipient cells. Recent studies revealed that miRNAs could control the progression of multiple sclerosis (MS) via differentiation and function of T helper cells (Th).

Methods

Here, we investigated the therapeutic effects of syngeneic-derived BM-MSC in experimental autoimmune encephalomyelitis (EAE) mouse model of MS by evaluating expression profile of miRNAs, pro- and anti-inflammatory in serum and brain tissues. Three-time scheme groups (6th day, 6th & 12th days, and 12th day, of post-EAE induction) were applied to determine the therapeutic effects of intraperitoneally received 1*106 of BM-MSCs.

Results

The expression levels of mature isoforms of miR-193, miR-146a, miR-155, miR-21, and miR-326 showed that BM-MSCs treatment attenuated the EAE clinical score and reduced clinical inflammation as well as demyelination. The improved neurological functional outcome associated with enhanced expression of miR-193 and miR-146a, but decreased expression levels of miR-155, miR-21, and miR-326 were followed by suppressing effects on Th1/Th17 immune responses (reduced levels of IFN-\(\gamma\)and IL-17 cytokine expression) and induction of Treg cells, immunoregulatory responses (increase of IL-10, TGF-β, and IL-4) in treatment groups.

Conclusion

Our findings suggest that BM-MSCs administration might change expression patterns of miRNAs and downstream interactions followed by immune system modulation. However, there is a need to carry out future human clinical trials and complementary experiments.

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Funding

This research was funded by grant no. 1587 from Semnan University of Medical Sciences (SEMUMS) research council.

Author information

Authors and Affiliations

  1. Cancer Research Center, Semnan University of Medical Sciences, Semnan, Iran

    Dariush Haghmorad & Bahman Yousefi

  2. Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran

    Dariush Haghmorad, Abdolvahid Sadeghnejad, Mahdieh Tarahomi & Bahman Yousefi

  3. Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Ali Khaleghian

  4. Department of Bacteriology and Virology, Semnan University of Medical Sciences, Semnan, Iran

    Majid Eslami

Authors
  1. Dariush Haghmorad
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  2. Ali Khaleghian
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  4. Abdolvahid Sadeghnejad
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  5. Mahdieh Tarahomi
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Contributions

All authors contributed to the study conception and design. BY and DH methodology; A. K. software; A. S. validation; M. E. M. T. and M. D. formal analysis; (A) K. investigation; M. T writing-original draft preparation; V. O. writing-review and editing, DH; (B) Y. project administration. All authors have read and agreed to the final version of the manuscript.

Corresponding author

Correspondence to Bahman Yousefi.

Ethics declarations

Ethics approval and consent to participate

All experiments were carried out in agreement with protocols approved by the ethics committee of Semnan University of Medical Sciences in Semnan, Iran (IRCT: IR.SEMUMS.REC.1398.46, ID: 1587).

Conflict of interest

All authors declare no financial or commercial conflict of interest; none have any non-financial conflict of interest.

DOI and license of Preprint

Posted Date: January 25th, 2022 DOI: https://doi.org/10.21203/rs.3.rs-1260157/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License.

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Haghmorad, D., Khaleghian, A., Eslami, M. et al. Bone marrow mesenchymal stem cells to ameliorate experimental autoimmune encephalomyelitis via modifying expression patterns of miRNAs. Mol Biol Rep 50, 9971–9984 (2023). https://doi.org/10.1007/s11033-023-08843-1

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