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Glial Response to Intranasal Mesenchymal Stem Cells in Intermittent Cuprizone Model of Demyelination

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Abstract

Intranasal mesenchymal stem cells (MSCs) delivery is a non-invasive method that has received interests for treatment of neurodegenerative diseases, such as multiple sclerosis (MS). The impact of intranasal MSCs on intermittent cuprizone model of demyelination was a focus of this study. C57/BL6 mice were fed with 0.3% cuprizone in an intermittent or single ways. Luxol fast blue (LFB), Rotarod test, quantitative real‐time polymerase chain reaction (qRT-PCR), immunohistochemistry and western blot (WB) were used for interpretation of outcomes. MSCs effectively homed to the corpus callosum area, were able to improve motor coordination and to promote myelin recovery in the intermittent cuprizone (INTRCPZ/MSCs). Astrogliosis (GFAP+ cells) and microgliosis (Iba-1+ cells) were hampered, and more mature oligodendrocyte cells (APC+ cells) were identified in mice receiving INTRCPZ/MSCs. Such treatment also considerably reduced markers related to the macrophage type 1 (M1) cells, namely iNOS and CD86, but it recovered the M2 markers MRC-1 and TREM-2. In addition, a remarkable decrease in the expressions of pro-inflammatory IL-1β and TNFα but an increase in the rate of anti-inflammatory TGF-β and IL-10 were identified in mice that underwent INTRCPZ/MSCs therapy. Finally, microvascular changes were evaluated, and a noticeable increase in the expression of the endothelial cell marker CD31 was found in the INTRCPZ/MSCs-treated mice (p < 0.05 for all). The outcomes are representative of the efficacy of intranasal MSCs delivery in intermittent cuprizone model of MS for reshaping macrophage polarity along with modification of glial, inflammatory, and angiogenic markers in favor of therapy.

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All data generated or analysed during this study are included in this published article.

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Funding

This study was supported by Tehran University of Medical Sciences (grant number: 99–2-140–49479).

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Authors and Affiliations

  1. Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Davood Zarini, Parichehr Pasbakhsh, Sina Mojaverrostami, Maedeh Hashemi, Shiva Amirizadeh & Iraj Ragerdi Kashani

  2. Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Shabani

  3. Department of Anatomy, School of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran

    Jamal Majidpoor

  4. Department of Anatomical Science, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Ameneh Omidi

  5. Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Keywan Mortezaee

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  1. Davood Zarini
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Contributions

All authors contributed distinctly in the presented work. Conceptualization and study designing, Iraj Ragerdi Kashani, Keywan Mortezae and Parichehr Pasbakhsh; Performing Experiments and data interpretation, Davood Zarini and Iraj Ragerdi Kashani; writing, original draft preparation, Davood Zarini, Sina Mojaverrostami and Maedeh Hashemi; review and editing, Shiva Amirizadeh, Jamal Majidpoor and Ameneh Omidi. Authors have read and agreed to publish of the manuscript.

Corresponding authors

Correspondence to Keywan Mortezaee or Iraj Ragerdi Kashani.

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Ethics Approval

All animal-related procedures, including anesthesia and surgery, were carried out according to the national and institutional guidelines of Tehran University of Medical Science for use and care of animals in the laboratory (ethical approval code: IR.TUMS.MEDICINE.REC.1399.237).

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Zarini, D., Pasbakhsh, P., Shabani, M. et al. Glial Response to Intranasal Mesenchymal Stem Cells in Intermittent Cuprizone Model of Demyelination. Neurotox Res 40, 1415–1426 (2022). https://doi.org/10.1007/s12640-022-00556-w

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