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