Molecular Biology Reports

, Volume 46, Issue 6, pp 6135–6146 | Cite as

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

  • Rahim Heidari Barchi Nezhad
  • Fateme Asadi
  • Seyyed Meysam Abtahi Froushani
  • Gholamhossein Hassanshahi
  • Ayat Kaeidi
  • Soudeh Khanamani Falahati-pour
  • Zahra Hashemi
  • Mohammad Reza MirzaeiEmail author
Original Article


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.


17-b estradiol Mesenchymal stem cells Experimental autoimmune encephalomyelitis Multiple sclerosis 



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


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.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Rahim Heidari Barchi Nezhad
    • 1
  • Fateme Asadi
    • 2
  • Seyyed Meysam Abtahi Froushani
    • 3
  • Gholamhossein Hassanshahi
    • 1
  • Ayat Kaeidi
    • 4
  • Soudeh Khanamani Falahati-pour
    • 5
  • Zahra Hashemi
    • 6
  • Mohammad Reza Mirzaei
    • 1
    Email author
  1. 1.Molecular Medicine Research Center, Research Institute of Basic Medical SciencesRafsanjan University of Medical SciencesRafsanjanIran
  2. 2.Department of Biochemistry, Faculty of MedicineRafsanjan University of Medical SciencesRafsanjanIran
  3. 3.Department of Microbiology, Faculty of Veterinary MedicineUrmia UniversityUrmiaIran
  4. 4.Physiology-Pharmacology Research CenterRafsanjan University of Medical SciencesRafsanjanIran
  5. 5.Pistachio Safety Research CenterRafsanjan University of Medical SciencesRafsanjanIran
  6. 6.Department of General SubjectsRafsanjan University of Medical SciencesRafsanjanIran

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