The Effect of Exosomes Isolated from Poly (I:C) Treated Human Wharton's Jelly Mesenchymal Stem Cells on CD4+CD25+Foxp3+ Regulatory T Cells

Ava Misaghian; Ata A Ghadiri; Ali Asadirad; Sareh Amirzadeh; Afshin Amari

doi:10.18502/ijaai.v23i3.15638

Ava Misaghian Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran
Ata A Ghadiri Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran
Ali Asadirad Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran
Sareh Amirzadeh Department of Infertility, Infertility Research and Treatment Center of ACECR, Ahvaz, Iran
Afshin Amari Department of Immunology, School of Medicine Ahvaz Jundishapur University of Medical sciences, Ahvaz, Iran

DOI: https://doi.org/10.18502/ijaai.v23i3.15638

Keywords: Exosome; Mesenchymal stem cells; Regulatory T-cells; Toll-like receptor3

Abstract

Mesenchymal stem cells (MSCs) are a potential cell therapy candidate for autoimmune and inflammatory diseases due to their multilineage capacity and immune modulating function. MSCs exert immunomodulatory effects on target cells through the secretion of exosomes. Inflammatory conditions such as Toll-like receptors (TLRs) engagement can change the biological functions and immunomodulatory activities of MSCs and the contents of exosomes derived from MSCs are changed. Regulatory T-cells (Treg) are crucial for maintaining immune cell homeostasis and self-tolerance. Our study aimed to investigate the impact of isolated exosomes from hWJ-MSCs that were treated with Poly (I:C) on regulatory CD4 CD25 Foxp3 T-cells.

MSCs were harvested from human umbilical cord Wharton’s Jelly by explant method. Stem cells were treated by Polyinosinic-polycytidylic acid sodium salt (Poly (I:C)) for 48 hours. Exosomes were extracted from supernatant of cells and Scanning electron microscopy (SEM) and Dynamic light scattering (DLS) were performed for them. Peripheral blood mononuclear cells (PBMCs) isolated from the healthy donors were stimulated with PHA (Phytohemagglutinin) and co-cultured with Poly (I:C) treated hWJ-MSCs derived exosome and untreated hWJ-MSCs derived exosome or without hWJ-MSCs-derived exosome for 6 days. Then, frequency of CD4+CD25+ Foxp3+ regulatory T cells was measured by flow cytometry.

Our results showed that exosomes isolated from Poly (I:C) treated hWJ-MSCs significantly increased frequency of CD4+CD25+ Foxp3+ regulatory T cells compared to the untreated hWJ-MSCs derived exosome group and control group.

Stimulation by TLR3 improved the anti-inflammatory features of exosomes that were derived from hWJ-MSCs by increasing the frequency of Treg cells.