Abstract
A subset of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) developed a condition of hyper-inflammation, which can cause multi-organ damage and the more severe forms of coronavirus disease 2019 (COVID-19). Mesenchymal stem cells (MSCs) can promote tissue regeneration and modulate immune responses and, thus, have the rational requirements to be used to counteract SARS-CoV-2-induced pneumonia and hyper-inflammation. The aim of the present study was to gain insight into possible mechanisms of action of MSCs obtained from human dental pulp [dental pulp stem cells (DPSCs)] in COVID-19 patients. We investigated the concentrations of 18 cytokines in supernatants of peripheral blood mononuclear cells (PBMCs) obtained from COVID-19 patients cultured in vitro alone and in contact with DPSCs. The modulation of cytokines in PBMCs was confirmed by real-time PCR. IL-6 was the sole cytokine detected in supernatants of DPSCs. In resting conditions, co-culture increased IL-1β, IL-2, IL-5, IL-6, IL-10, IL-18, TNFα, and granulocyte macrophage colony-stimulating factor (GM-CSF) levels. When PBMCs were activated with anti-CD3/CD28 antibody-coated beads, co-culture increased IL-6 and GM-CSF, whereas it decreased IFNγ, TNFα, IL-2, IL-5, IL-9, IL-10, IL-12 (p70), IL-17A, IL-18, IL-21, IL-23, and IL-27 levels. Concentrations of IL-1β, IL-4, IL-13, and IL-22 were not affected. The comparison of cytokine concentrations in supernatants of PBMCs from COVID-19 patients vs. healthy subjects revealed lower concentrations of IL-10 and higher concentrations of IL-18 in supernatants of CD3/CD28-activated PBMCs from COVID-19 patients. Results are explorative but indicate that DPSCs can modulate the production of cytokines deregulated in COVID-19 patients, supporting their potential use in COVID-19.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the agent responsible for the coronavirus disease 2019 (COVID-19)
We investigated gene expression of the cytokines, which resulted modulated in supernatants from all the samples (TNFα, IL-12, IL-21, IL-23, and IL-6) and/or are relevant for COVID-19 (IL-10, IL-17, and IFNγ)
To determine the effects of dental pulp stem cells (DPSCs) on peripheral blood mononuclear cells (PBMCs) from COVID-19 patients, PBMCs were added to DPSCs monolayer at 10:1 ratio and co-cultured for 48 h
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the agent responsible for the coronavirus disease 2019 (COVID-19). It is a betacoronavirus, endowed with envelope and single-stranded RNA genome. In a subset of patients, a condition of hyper-inflammation characterized by the production of several cytokines and excessive immune cell infiltration into tissues occur, causing multi-organ damage and severe COVID-19 (Tay et al, 2020). Evidences on the pathogenic role of host immune responses in SARS-CoV-2 infection represent the rationale for testing the efficacy of anti-inflammatory and immunosuppressive drugs/products in COVID-19 patients who show hyper-inflammation (Calabrese, 2020; Rizk et al, 2020)
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