Exosomes from Adipose Tissue-derived Mesenchymal Stem Cells Induce Regulatory T Cells in COVID‐19 Patients

Morteza Motallebnezhad; Ali Hazrati; Hadi Esmaeili Gouvarchin Ghaleh; Nematollah Jonaidi-Jafari; Sanaz  Abbaspour-Aghdam; Kosar Malekpour; Mehdi Yousefi; Hossein Samadi Kafil; Farhad  Jadidi-Niaragh; Leila Roshangar; Hamed Valizadeh; Morteza Izadi; Majid Ahmadi

doi:10.18502/ijaai.v22i3.13051

Morteza Motallebnezhad Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Ali Hazrati Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Hadi Esmaeili Gouvarchin Ghaleh Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Nematollah Jonaidi-Jafari Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Sanaz Abbaspour-Aghdam Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Kosar Malekpour Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
Mehdi Yousefi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Hossein Samadi Kafil Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Farhad Jadidi-Niaragh Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Leila Roshangar Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Hamed Valizadeh Tuberculosis and Lung Disease Research Center of Tabriz University of Medical Sciences, Tabriz, Iran
Morteza Izadi Health Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
Majid Ahmadi Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

DOI: https://doi.org/10.18502/ijaai.v22i3.13051

Keywords: COVID-19; Exosomes; Immunomodulation; Mesenchymal stem cells; Peripheral blood mononuclear cells; Regulatory T cells

Abstract

An imbalance between regulatory T (Treg) and T-helper (Th)-17 cells has been implicated in the pathogenesis of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) exert immunomodulatory properties through secreting exosomes. This study aimed to assess the effect of MSC-derived exosomes (MSC-Exo) on the differentiation of peripheral blood mononuclear cells (PBMCs) into Tregs from patients with COVID-19.

Exosomes were isolated from adipose tissue–derived MSCs. PBMCs were separated from the whole blood of COVID-19 patients (n=20). Treg frequency was assessed before and 48 hours after treatment of PBMCs with MSC-Exo using flow cytometry. Expression of FOXP3 and cytokine genes, and the concentration of cytokines associated with Tregs, were assessed before and after treatment with MSC-Exo.

The frequency of CD4⁺CD25⁺CD127^- Tregs was significantly higher after treating PBMCs with MSC-Exo (6.695±2.528) compared to before treatment (4.981±2.068). The expressions of transforming growth factor (TGF)-β1, interleukin (IL)-10, and FOXP3 were significantly upregulated in MSC-Exo–treated PBMCs. The concentration of IL‐10 increased significantly
after treatment (994.7±543.9 pg/mL) of PBMCs with MSC-Exo compared with before treatment (563.5±408.6 pg/mL). The concentration of TGF-β was significantly higher in the supernatant

of PBMCs after treatment with MSC-Exo (477.0±391.1 pg/mL) than PBMCs before treatment (257.7±226.3 pg/mL).

MSC-Exo has the potential to raise anti-inflammatory responses by induction of Tregs, potentiating its therapeutic effects in COVID-19.