Croci Stefania, Bonacini Martina, Dolci Giovanni, Massari Marco, Facciolongo Nicola, Pignatti Elisa, Pisciotta Alessandra, Carnevale Gianluca, Negro Aurelio, Cassone Giulia, Muratore Francesco, Belloni Lucia, Zerbini Alessandro, Salvarani Carlo
Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Infectious Disease Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
Front Cell Dev Biol. 2021 Feb 5;8:609204. doi: 10.3389/fcell.2020.609204. eCollection 2020.
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 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.
一部分感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的患者出现了过度炎症状态，这可能导致多器官损伤以及更严重形式的2019冠状病毒病（COVID-19）。间充质干细胞（MSCs）可以促进组织再生并调节免疫反应，因此，有合理的需求将其用于对抗SARS-CoV-2引起的肺炎和过度炎症。本研究的目的是深入了解从人牙髓中获得的间充质干细胞[牙髓干细胞（DPSCs）]在COVID-19患者中的可能作用机制。我们研究了从COVID-19患者中单独培养以及与DPSCs接触培养后获得的外周血单个核细胞（PBMCs）上清液中18种细胞因子的浓度。通过实时PCR证实了PBMCs中细胞因子的调节情况。IL-6是在DPSCs上清液中检测到的唯一细胞因子。在静息状态下，共培养增加了IL-1β、IL-2、IL-5、IL-6、IL-10、IL-18、TNFα和粒细胞巨噬细胞集落刺激因子（GM-CSF）的水平。当用抗CD3/CD28抗体包被的珠子激活PBMCs时，共培养增加了IL-6和GM-CSF，而降低了IFNγ、TNFα、IL-2、IL-5、IL-9、IL-10、IL-12（p70）、IL-17A、IL-18、IL-21、IL-23和IL-27的水平。IL-1β、IL-4、IL-13和IL-22的浓度未受影响。COVID-19患者与健康受试者PBMCs上清液中细胞因子浓度的比较显示，COVID-19患者CD3/CD28激活的PBMCs上清液中IL-10浓度较低，IL-18浓度较高。结果具有探索性，但表明DPSCs可以调节COVID-19患者中失调的细胞因子产生，支持其在COVID-19中的潜在应用。
