Adv Pharm Bull. 2022;12(2): 389-397.
doi: 10.34172/apb.2022.038
  Abstract View: 488
  PDF Download: 188

Research Article

Immunomodulatory Potential of Human Mesenchymal Stem Cells and their Exosomes on Multiple Sclerosis

Hussein Baharlooi 1,2 ORCID logo, Zahra Salehi 1, Moein Minbashi Moeini 3,4, Nima Rezaei 1,5,6, Maryam Azimi 7* ORCID logo

1 Department of Immunology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
2 Students’ Scientific Center, Tehran University of Medical Sciences (TUMS), PO Box 1417755331, Tehran, Iran.
3 Department of Physiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
4 Faculty of Pharmacy, Université Laval, Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec (CRIUCPQ), Québec, Canada.
5 Research Center for Immunodeficiencies, Children’s Medical Center, Tehran University of Medical Sciences (TUMS), Tehran, Iran.
6 Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
7 Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences (IUMS), Tehran, Iran.
*Corresponding Author: Maryam Azimi, Tel: 021-64352659, Fax: 021-66554063,Email: azimi.mr@iums.ac.ir


Purpose: Promising advances have been made in mesenchymal stem cell transplantation to reinducethe immune tolerance in neuroinflammatory animal models and multiple sclerosis (MS)patients. The available evidence demonstrated that immunomodulatory effects of mesenchymalstem cell are particularly exerted through releasing exosomes to their environment. Wetherefore, aimed to comparatively assess the potential effect of mesenchymal stem cells andmesenchymal stem cells-derived exosomes on proliferation and function of the CD4+CD25−conventional T cells, isolated from relapsing-remitting MS patients.Methods: Mesenchymal stem cells were isolated from human umbilical cord tissues and usedfor exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymalstem cells-derived exosomes were evaluated for their anti-inflammatory effects againstthe proliferation of T cells isolated from two groups of individuals in vitro, MS patients andhealthy subjects. Cytokine production of conventional T cells (interferon-γ, interleukin-10, andinterleukin-17) was also assessed, using flow cytometry for the patients and healthy individuals.Results: Here, evidence shows that MSCs and MSC-derived exosomes dampen proliferationand percentage of conventional T cells that produce IFN-γ (healthy control: P<0.001) andinterleukin-17 (healthy control: P <0.001, MS patients: P <0.001), with a significant increaseof IL-10 producing cells in the patients and healthy individuals. Surprisingly, MSC-derivedexosomes demonstrated higher immune-modulating properties on conventional T cellsresponses, compared to mesenchymal stem cells (MSCs).Conclusion: The current study, provides a novel approach of exocytosis on autoimmune therapy.In particular, Mesenchymal stem cell -derived exosomes, which are cell-derived biologics,could be considered as an alternative for Mesenchymal stem cells in treating MS.
Keywords: Relapsing-remitting MS, Mesenchymal stem cell, Exosome, Immunomodulation

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Submitted: 10 Aug 2020
Revision: 04 Dec 2020
Accepted: 05 Feb 2021
ePublished: 06 Feb 2021
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