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Genetically Engineered Mesenchymal Stem Cell Therapy Against Murine Experimental Autoimmune Encephalomyelitis

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Abstract

We used recombinant interleukin 23 receptor (RIL-23R)-engineered mesenchymal stem cells (MSCs) to study its therapeutic role in enhancing inflammation of nervous tissue in the mouse model (EAE) of multiple sclerosis (MS). Recombinant IL-23 receptor construct was designed to enter MSCs. The bioactivity of the constructs was assessed by the co-culture of MSCs/CD4 + T cells. The EAE model was induced in mice. After cell transplantation, clinical scores were evaluated, and tissue demyelination was measured by Luxol fast blue staining. The transfection of RIL-23R mRNA improved MSC properties significantly to the inflamed regions of EAE mice, and it performed an increased suppressive function on the T lymphocyte proliferation. Furthermore, in vivo therapy with RIL-23R MSCs in EAE mice showed an enhanced therapeutic action than MSCs, proven by improved myelination and a reduction in the penetration of inflammatory cells into the white matter. Our targeted transplantation procedure of modified MSC can be applied to improve the effectiveness of cellular therapy for multiple sclerosis and other autoimmune disorders.

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Data Availability

The dataset supporting the conclusions of this paper is included within the paper (and its additional file(s)).

Abbreviations

EAE:

Experimental autoimmune encephalomyelitis

MS:

Multiple sclerosis

MSCs:

Mesenchymal stem cells

TGF-Β:

transforming growth factor beta

PHA:

phytohaemagglutinin

GAPDH:

glyceraldehyde-3-phosphate dehydrogenase

LFB:

Luxol fast blu

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Acknowledgements

We are grateful to the Golestan University of Medical Sciences and AryaTinaGene (ATG) Biopharmaceutical Company for their funding.

Funding

This study was supported by grants from –the Research and Technology Council of Golestan University of Medical Sciences (Grant No. 940805182).

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Authors and Affiliations

  1. Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran

    Masoumeh Rostami, Kamran Haidari, Hossein Amini & Majid Shahbazi

  2. Department of Immunotherapy and Leishmania Vaccine Research, Pasteur Institute of Iran, Tehran, Iran

    Masoumeh Rostami

  3. Department of Anatomical Sciences, Golestan University of Medical Sciences, Gorgan, Iran

    Kamran Haidari

  4. AryaTinaGene Biopharmaceutical Company, Gorgan, Iran

    Hossein Amini & Majid Shahbazi

Authors
  1. Masoumeh Rostami
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  2. Kamran Haidari
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  3. Hossein Amini
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  4. Majid Shahbazi
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Contributions

Majid Shahbazi designed, supervised the project, and edited the paper. Masoumeh Rostami performed laboratory experiments and data analysis. Besides, Kamran Haidari supervised the laboratory experiments. The present work is a result of co-writing of these people together with Hossein Amini.

Corresponding author

Correspondence to Majid Shahbazi.

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The present study was approved by the ethics committee of the Golestan University of Medical Sciences.

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Authors consent to publish identifiable details within the text in the journal of molecular neurobiology.

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The authors declare no competing interests.

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Rostami, M., Haidari, K., Amini, H. et al. Genetically Engineered Mesenchymal Stem Cell Therapy Against Murine Experimental Autoimmune Encephalomyelitis. Mol Neurobiol 59, 3449–3457 (2022). https://doi.org/10.1007/s12035-022-02774-x

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  • DOI: https://doi.org/10.1007/s12035-022-02774-x

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