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Human Dental Pulp Stem Cells Modulate Cytokine Production in vitro by Peripheral Blood Mononuclear Cells From Coronavirus Disease 2019 Patients.

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-1?, IL-2, IL-5, IL-6, IL-10, IL-18, TNF?, 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 IFN?, TNF?, 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-1?, 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.

SUBMITTER: Croci S

PROVIDER: S-EPMC7901970 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Human Dental Pulp Stem Cells Modulate Cytokine Production <i>in vitro</i> by Peripheral Blood Mononuclear Cells From Coronavirus Disease 2019 Patients.

Croci Stefania S Bonacini Martina M Dolci Giovanni G Massari Marco M Facciolongo Nicola N Pignatti Elisa E Pisciotta Alessandra A Carnevale Gianluca G Negro Aurelio A Cassone Giulia G Muratore Francesco F Belloni Lucia L Zerbini Alessandro A Salvarani Carlo C

Frontiers in cell and developmental biology 20210205

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 insig ...[more]

PMID: 33634100

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Project description:BACKGROUND:Nerve diseases and injuries, which are usually accompanied by motor or sensory dysfunction and disorder, impose a heavy burden upon patients and greatly reduce their quality of life. Dental pulp stem cells (DPSCs), derived from the neural crest, have many characteristics that are similar to those of neural cells, indicating that they can be an ideal source for neural repair. AIM:To explore the potential roles and molecular mechanisms of DPSCs in crushed nerve recovery. METHODS:DPSCs were isolated, cultured, and identified by multilineage differentiation and flow cytometry. Western blot and immunofluorescent staining were applied to analyze the expression levels of neurotrophic proteins in DPSCs after neural induction. Then, we collected the secretions of DPSCs. We analyzed their effects on RSC96 cell proliferation and migration by CCK8 and transwell assays. Finally, we generated a sciatic nerve crush injury model in vivo and used the sciatic function index, walking track analysis, muscle weight, and hematoxylin & eosin (H&E) staining to further evaluate the nerve repair ability of DPSCs. RESULTS:DPSCs highly expressed several specific neural markers, including GFAP, S100, Nestin, P75, and NF200, and were inclined toward neural differentiation. Furthermore, neural-induced DPSCs (N-DPSCs) could express neurotrophic factors, including NGF, BDNF, and GDNF. The secretions of N-DPSCs could enhance the proliferation and migration of Schwann cells. In vivo, both DPSC and N-DPSC implants alleviated gastrocnemius muscle atrophy. However, in terms of anatomy and motor function, as shown by H&E staining, immunofluorescent staining, and walking track analyses, the repair effects of N-DPSCs were more sustained, potent, and effective than those of DPSCs and the controls. CONCLUSION:In summary, this study demonstrated that DPSCs are inclined to differentiate into neural cells. N-DPSCs express neurotrophic proteins that could enhance the proliferation and migration of SCs. Furthermore, our results suggested that N-DPSCs could help crushed nerves with functional recovery and anatomical repair in vivo. Thus, DPSCs or N-DPSCs could be a promising therapeutic cell source for peripheral nerve repair and regeneration.

Project description:BackgroundDental pulp stem cells (DPSCs) have been developed as a potential source of mesenchymal stem cells (MSCs) for regeneration of dental pulp and other tissues. However, further strategies to isolate highly functional DPSCs beyond the colony-forming methods are required. We have demonstrated the safety and efficacy of DPSCs isolated by G-CSF-induced mobilization and cultured under normoxia (mobilized DPSCs, MDPSCs) for pulp regeneration. The device for isolation of MDPSCs, however, is not cost-effective and requires a prolonged cell culture period. It is well known that MSCs cultured under hypoxic-preconditions improved MSC proliferation activity and stemness. Therefore, in this investigation, we attempted to improve the clinical utility of DPSCs by hypoxia-preconditioned DPSCs (hpDPSCs) compared with MDPSCs to improve the potential clinical utility for pulp regeneration in endodontic dentistry.MethodsColony-forming DPSCs were isolated and preconditioned with hypoxia in a stable closed cultured system and compared with MDPSCs isolated from the individual dog teeth. We examined the proliferation rate, migration potential, anti-apoptotic activity, and gene expression of the stem cell markers and angiogenic/neurotrophic factors. Trophic effects of the conditioned medium (CM) were also evaluated. In addition, the expression of immunomodulatory molecules upon stimulation with IFN-γ was investigated. The pulp regenerative potential and transplantation safety of hpDPSCs were further assessed in pulpectomized teeth in dogs by histological and immunohistochemical analyses and by chemistry of the blood and urine tests.ResultshpDPSCs demonstrated higher proliferation rate and expression of a major regulator of oxygen homeostasis, HIF-1α, and a stem cell marker, CXCR-4. The direct migratory activity of hpDPSCs in response to G-CSF was significantly higher than MDPSCs. The CM of hpDPSCs stimulated neurite extension. However, there were no changes in angiogenic, migration, and anti-apoptotic activities compared with the CM of MDPSCs. The expression of immunomodulatory gene, PTGE was significantly upregulated by IFN gamma in hpDPSCs compared with MDPSCs. However, no difference in nitric oxide was observed. The regenerated pulp tissue was quantitatively and qualitatively similar in hpDPSC transplants compared with MDPSC transplants in dog teeth. There was no evidence of toxicity or adverse events of the hpDPSC transplantation.ConclusionsThese results demonstrated that the efficacy of hpDPSCs for pulp regeneration was identical, although hpDPSCs improved stem cell properties compared to MDPSCs, suggesting their potential clinical utility for pulp regeneration.

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Human Dental Pulp Stem Cells Modulate Cytokine Production in vitro by Peripheral Blood Mononuclear Cells From Coronavirus Disease 2019 Patients.

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Human Dental Pulp Stem Cells Modulate Cytokine Production <i>in vitro</i> by Peripheral Blood Mononuclear Cells From Coronavirus Disease 2019 Patients.

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