Objective: Dental mesenchymal stem cells (MSCs) are potential for use in tissue regeneration in inflammatory diseases due to their rapid proliferating, multilineage differentiation, and strong anti-inflammatory features. In the present study, immunoregulatory and glandular tissue regeneration effects of the dental follicle (DF)MSCs in Sjögren’s Syndrome (SS) were investigated. Methods: Dental follicle (DF) tissues were obtained from healthy individuals during tooth extraction, tissues were digested enzymatically and DFMSCs were cultured until the third passage. DFMSCs were labeled with Quantum dot 655 for cell tracking analysis. The induction of the SS mouse model was performed by the injection of Ro60-273-289 peptide intraperitoneally. DFMSCs were injected intraperitoneally, or into submandibular, or lacrimal glands. Splenocytes were analyzed for intracellular cytokine (IFN-γ, IL-17, IL-10) secretion in T helper cells, lymphocyte proliferation, and B lymphocyte subsets. Histologic analysis was done for submandibular and lacrimal glands with hematoxylin-eosin staining for morphologic examination. Results: The systemic injection of DFMSCs significantly reduced intracellular IFN-γ and IL-17 secreting CD4+ T cells in splenocytes (p<0.05), and decreased inflammatory cell deposits and fibrosis in the glandular tissues. DFMSCs differentiated to glandular epithelial cells in submandibular and lacrimal injections with a significant reduction in lymphocytic foci. The results showed that few amounts of DFMSCs were deposited in glandular tissues when applied intraperitoneally, while high amounts of DFMSCs were located in glandular tissues and differentiated to glandular epithelial cells when applied locally in SS murine model. Conclusion: DFMSCs have the potential for the regulation of Th1, Th17, and Treg balance in SS, and ameliorate glandular dysfunction. DFMSCs can be a beneficial therapeutic application for SS.

Background/Aims: Crohn’s Disease (CD) is a chronic inflammatory condition characterized by various abnormalities that lead to overly aggressive T-cell responses. Our in vitro experiments aimed to investigate the potential use of Dental Follicle Mesenchymal Stem Cells (DF-MSCs) to suppress the exaggerated immune response in inflamed and non-inflamed tissue of Crohn’s Disease (CD). Material and Methods: Dental follicle tissues were obtained from extracted third molar teeth of 3 healthy volunteers who have no abscess or inflammatory diseases. Eleven patients included the experiment who had been diagnosed with CD and not received steroid maintenance therapy for more than 1 month. Mononuclear Cells (MNCs) were isolated from inflamed and non-inflamed tissue of CD. Isolated cells were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the presence and absence of DF-MSCs and analyzed for lymphocytes proliferation capacity and viability, T lymphocyte subsets, CD4+IL22BP and CD4+CD25+Foxp3+ regulatory T cell (Tregs) frequencies and cytokine levels. Results: A significant downregulation of lymphocyte proliferation and CD4+IL22BP T cell ratio were found in inflamed cultures with DF-MSCs (p<0,005). Also, the frequency of Tregs increased with DF-MSCs (p<0,05). Pro-inflammatory cytokine levels (TNF-α and IL-6) were decreased (p<0,05) and IL-10 levels were increased (p<0,05) in the supernatant of inflamed cultures. Conclusion: DF-MSCs reduced the inflammatory immune response, induced Tregs and downregulated CD4+IL22BP T cell ratio in inflamed samples of CD patients, which may be exploited for significant therapeutic use.

Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder. The advancements in the understanding of AD immunological pathogenesis have caused the development of therapies that suppre... Lay abstract Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. There is no definite solution ...

Background: In this article, the authors investigate the modulatory effects of dental mesenchymal stem cells (MSCs) on lymphocyte responses in primary Sjögren's syndrome (pSS), which is an autoimmu... Plain language summary In this article, the authors investigate the modulatory effects of dental mesenchymal stem cells (dental MSCs) on lymphocyte responses in primary Sjögren's syndrome (pSS), wh...

Multipotent mesenchymal stem cells (MSCs) have been investigated in autoimmune diseases such as rheumatoid arthritis (RA) due to their immunomodulatory and regenerative properties. In this study, their immunosuppressive effects on peripheral blood mononuclear cells (PBMC) of RA patients were studied. Dental Follicle Stem Cells (DFSCs) were isolated from follicle tissue in the orofacial region. Characterization and multipotency analyses were performed. Lymphocytes were isolated from peripheral venous blood of RA patients (n=5) and healthy individuals (n=5). DFSCs were pre-incubated with IFN-? for 48 hr. PBMCs of RA patients and healthy individuals were separately cultured with or without DFSCs for 72 hours. After the culture period, lymphocyte proliferation and viability, the frequency of CD4+ CD25+FoxP3+ T regulatory cells, IL-10 and TNF-? levels in the culture supernatants were measured via flow cytometry. Our results demonstrated that DFSCs suppressed proliferation of T lymphocytes by increasing the number of FoxP3 expressing CD4+CD25+ T regulatory cells and suppressed lymphocyte apoptosis in RA patients. Also, DFSCs reduced TNF-? cytokine secretion and upregulated IL-10 secreting cells. Such cells could potentially be a source for future immunomodulatory treatments of RA patients.