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.
【저자키워드】 COVID-19, SARS-CoV-2, immunomodulation, Mesenchymal stem cells, cytokine, interleukin, dental pulp stem cells, 【초록키워드】 coronavirus disease, Macrophage, coronavirus, immune response, IL-17A, Pneumonia, IL-6, GM-CSF, MSCs, in vitro, Peripheral blood, Real-time PCR, Patient, hyper-inflammation, PBMC, IL-10, mesenchymal stem cell, mechanism, COVID-19 patients, IL-2, IL-21, IL-13, IL-4, IL-22, IL-1β, Concentration, PBMCs, MSC, Contact, COVID-19 patient, Multi-organ damage, stem cell, granulocyte, mononuclear cell, acute respiratory syndrome, tissue regeneration, modulation, IFNγ, DPSCs, TNFα, IL-12, IL-5, supernatant, IL-18, IL-23, IL-27, co-culture, IL-9, Result, investigated, form, activated, modulate, promote, not affected, subset, conditions, healthy subject, deregulated, DPSC, 【제목키워드】 Production, Human, in vitro, dental, peripheral, STEM, Pulp,