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The effects of transplanted mesenchymal stem cells treated with 17-b estradiol on experimental autoimmune encephalomyelitis

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Abstract

The present study was conducted aimed at exploring the modulatory effects of 17-b estradiol (17-bED) on mesenchymal stem cells (MSCs) in the EAE (experimental autoimmune encephalomyelitis) animal model of multiple sclerosis (MS). Following the isolation of bone marrow-derived MSCs from the bilateral femurs and tibias of the male Wistar rats, the cells were harvested and cultured in the presence of 100 nM 17-bED for 24 h. EAE was induced in male Wistar rats (8–12 weeks old) using guinea pig spinal cord homogenate, in combination with the complete Freund’s adjuvant. The MSC therapy was triggered when all of the animals obtained a disability score. The symptoms were monitored on a daily basis throughout the study until the rats were euthanized. The mRNA expression of cytokines, including IL-17, IFN-γ, TNF-α, IL-10, IL-4, and TGF-β together with MMP8 and MMP9 as the family members of matrix metalloproteinases (MMPs) in the brain and spinal cord tissues were examined using real-time PCR. The levels of splenocytes-originated IL-10 and IFN-γ cytokines were also measured by ELISA. The MTT-based research findings showed that the infiltration of lymphocytes into the spleen decreased considerably. It was also observed that the mRNA expression of proinflammatory cytokines decreased significantly, while the mRNA levels of anti-inflammatory cytokines increased remarkably. It was also found that the mRNA levels of the examined matrix metalloproteinases (MMP8 and MMP9) were downregulated significantly. The findings of the present study indicated that the administration of 17-bED enhanced the efficacy of MSCs transplantation and modulated immune responses relatively in the EAE model, via the regulation of either pro- or anti-inflammatory cytokines and matrix metalloproteinases.

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Acknowledgements

The authors would like to express their sincere gratitude to Rafsanjan University of Medical Sciences, Rafsanjan, Iran, for its great support of this study.

Funding

This study was supported by the RUMS by the Grant Number “1396.11.7-1535” and ethical code “IR.RUMS.REC.1396.165” from the Rafsanjan University of Medical Sciences.

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Authors and Affiliations

  1. Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, 7718175911, Iran

    Rahim Heidari Barchi Nezhad, Gholamhossein Hassanshahi & Mohammad Reza Mirzaei

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

    Fateme Asadi

  3. Department of Microbiology, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran

    Seyyed Meysam Abtahi Froushani

  4. Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Ayat Kaeidi

  5. Pistachio Safety Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Soudeh Khanamani Falahati-pour

  6. Department of General Subjects, Rafsanjan University of Medical Sciences, Rafsanjan, Iran

    Zahra Hashemi

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  1. Rahim Heidari Barchi Nezhad
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Correspondence to Mohammad Reza Mirzaei.

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Heidari Barchi Nezhad, R., Asadi, F., Abtahi Froushani, S.M. et al. The effects of transplanted mesenchymal stem cells treated with 17-b estradiol on experimental autoimmune encephalomyelitis. Mol Biol Rep 46, 6135–6146 (2019). https://doi.org/10.1007/s11033-019-05048-3

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