Placental Extract and Exosomes Derived from Pregnant Mice Attenuate the Development of Experimental Autoimmune Encephalomyelitis

Morteza Motallebnezhad; Shirin Taghizadeh; Tayebe Aghaie; Maryam Azimi; Ali-Akbar Salari; Mahmoud Bozorgmehr; Elahe Safari; Reza Falak; Mir Hadi Jazayeri

doi:10.18502/ijaai.v21i6.11525

Morteza Motallebnezhad Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Shirin Taghizadeh Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Tayebe Aghaie Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Maryam Azimi Immunology Research Center, Institute of Immunology and Infectious Disease, Iran University of Medical Sciences, Tehran, Iran
Ali-Akbar Salari Salari Institute of Cognitive and Behavioral Disorders (SICBD), Karaj, Alborz, Iran
Mahmoud Bozorgmehr Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, Iran
Elahe Safari Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Reza Falak Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Mir Hadi Jazayeri Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

DOI: https://doi.org/10.18502/ijaai.v21i6.11525

Keywords: Exosome; Experimental autoimmune encephalomyelitis; Glatiramer acetate; Multiple sclerosis; Placental extract

Abstract

Placental extract (PE) and exosomes from pregnant mice appear to have immunomodulatory and neuroprotective effects. In this study, we assessed the potential therapeutic effects of PE and exosomes obtained from pregnant mice in experimental autoimmune encephalomyelitis (EAE) mouse models.

C57BL/6 mice, 8 to 12 weeks of age, were prepared and administered PE, exosomes, and glatiramer acetate (GA), as an FDA-approved treatment for multiple sclerosis (MS), after EAE induction. Thereafter, the therapeutic effects of treatment were evaluated by measuring the clinical courses of the mice as well as determining the number of regulatory T (Treg) cells using flow cytometry, cytokine levels, and microRNA-326 expression via real-time PCR.

GA, PE, and exosomes reduced clinical severity, the extent of spinal cord demyelination, and the infiltration of inflammatory cells into the spinal cord. The frequency of CD4⁺CD25⁺FoxP3⁺ Treg cells increased after treatment of EAE mice with GA, PE, and exosomes. The mRNA expression of the inflammatory cytokines (interleukin-17 and interferon-gamma), as well as miR-326 expression, decreased significantly in the EAE mice after treatment with GA and exosomes.

PE and exosomes from pregnant mice are involved in the modulation of Treg/Th17 balance and provide a therapeutic approach for MS. Further clinical studies will hopefully confirm the safety and efficacy of such treatments in MS patients.