Cytotoxicity of Glass Ionomer Cement on Human Exfoliated Deciduous Teeth Stem Cells Correlates with Released Fluoride, Strontium and Aluminum Ion Concentrations

Stem cells from human exfoliated deciduous teeth (SHED) can be used as a cell-based therapy in regenerative medicine and in immunomodulation. Pulp from human deciduous teeth can be stored as a source of SHED. Glass ionomer cements (GICs) are commonly used in restorative dentistry and in cavity lining. GICs have lower biocompatibility and are cytotoxic for dental pulp cells. In this study, seven commonly used GICs were tested for their cytotoxic effects on SHED, for their potential to arrest mitosis in cells and induce chromosome aberrations, and were compared with the effects of composite. Fuji II, Fuji VIII, Fuji IX, Fuji plus and Vitrebond had significantly higher cytotoxic effects on SHED than composite. Only SHEDs that have been treated with Fuji I, Fuji IX, Fuji plus and composite recovered the potential for proliferation, but no chromosome aberrations were found after treatment with GICs. The cytotoxic effects of GICs on SHEDs were in strong correlation with combined concentrations of released fluoride, aluminum and strontium ions. Fuji I exhibited the lowest activity towards SHEDs; it did not interrupt mitosis and did not induce chromosome aberrations, and was accompanied by the lowest levels of released F, Al and Sr ions

The role of regulatory T cells in the modulation of anti-tumor immune response

It has been shown that the loss of regulatory function by deple­ + Regulatory T cells (Treg) represent a subset of CD4 T cells whose function is to suppress immune responses. Treg lymphocytes can be divided into two subsets: natural nTreg lymphocytes that are developed in the thymus and inducible iTreg lymphocytes, which originate from conventional T lymphocytes on the periphery. The majority of Treg lymphocytes express high levels of interleukin­2 (IL­2) receptor α chain (CD25) and transcription factor FoxP3 (critical for the development and suppressor activity of iTreg lymphocytes). Cancer cells can modulate anti­tumor immune response indirectly, through the activation of Treg lymphocytes. tion of tumor­induced Treg lymphocytes may enhance effectors response, resulting in tumor rejection, while the increased number of Treg lymphocytes effectively prevents tumor destruction. nTreg lymphocytes express increasingly CTLA­4 and membrane­ bound TGF­β, which inhibits cytokine production and responses of effectors lymphocytes. iTreg lymphocytes secrete immunosuppressive cytokines such as IL­10 and TGF­β. Treg lymphocytes represent one of important obstruction in anti­tumor immunity

Cytotoxicity of glass ionomer cement on human exfoliated deciduous teeth stem cells correlates with released fluoride, strontium and aluminum ion concentrations

Stem cells from human exfoliated deciduous teeth (SHED) can be used as a cell-based therapy in regenerative medicine and in immunomodulation. Pulp from human deciduous teeth can be stored as a source of SHED. Glass ionomer cements (GICs) are commonly used in restorative dentistry and in cavity lining. GICs have lower biocompatibility and are cytotoxic for dental pulp cells. In this study, seven commonly used GICs were tested for their cytotoxic effects on SHED, for their potential to arrest mitosis in cells and induce chromosome aberrations, and were compared with the effects of composite. Fuji II, Fuji VIII, Fuji IX, Fuji plus and Vitrebond had significantly higher cytotoxic effects on SHED than composite. Only SHEDs that have been treated with Fuji I, Fuji IX, Fuji plus and composite recovered the potential for proliferation, but no chromosome aberrations were found after treatment with GICs. The cytotoxic effects of GICs on SHEDs were in strong correlation with combined concentrations of released fluoride, aluminum and strontium ions. Fuji I exhibited the lowest activity towards SHEDs; it did not interrupt mitosis and did not induce chromosome aberrations, and was accompanied by the lowest levels of released F, Al and Sr ions. Projekat Ministarstva nauke Republike Srbije, br. ON175069, br. ON175071 i br. ON175103

The effect of dental caries and restorative biomaterials on IL-1 β and TNF-α levels in the gingival crevicular fluid

© 2021 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Background/Aim. In the spirit of personalized medicine, de-termining caries biomarkers in the saliva and gingival crevicular fluid (GCF) attracts great attention in the current dental re-search. The concentration of GCF cytokines is illustrative in depicting the processes in tooth structures. Their relevance must be inspected with aspects of tooth position and caries le-sion level. Different impacts of dental restoration materials on GCF IL-1β and TNF-α could be used as a parameter for esti-mating local inflammation. This paper aimed to estimate the concentrations of the proinflammatory cytokines (IL-1β and TNF-α) in the GCF and to correlate them with caries exten-sion, tooth position, and different restorative biomaterials. Methods. GCF samples were collected from 90 periodontally healthy patients demonstrating at least one tooth with proximal caries and one intact tooth, at the baseline, 7 and 30-days post-treatment. The biomarkers' profile was investigated in relation to different levels of caries extension (superficial, pulpitis, gan-grenous, root affection), defect size, and restorative biomaterial. Results. Before therapy, caries level was significantly associat-ed with GCF IL-1β concentration, demonstrating the lowest level in gangrenous (C4) and superficial caries (C2). Thirty days after therapy, root affection (C5) was characterized by the high-est IL-1β concentration. Different dental fillings showed vari-ous GCF cytokine changes. CPC induced a significant IL-1β increase in more than 70% of treated patients. Caries lesion size was insignificantly associated with GCF levels of these proin-flammatory cytokines, where larger defects were followed by an average cytokine increase. Considering the tooth position be-fore therapy, IL-1β had the highest level in GCF samples from caries-affected canines and second molars, while TNF-α showed the highest levels from canines GCF. Dental restora-tion induced cytokine increase in canines (IL-1β and TNF-α), 1st and 2nd molars GCF (IL-1β). Conclusion. Inflammation intensity of tooth structures was directly reflected in IL-1β and TNF-α concentrations. Dental restoration significantly affects IL-1β and TNF-α levels, depending on the used dental filling-type material. The profile of these cytokines varied in GCF samples of the tooth with different anatomical positions, where canines and molars demonstrated the highest level. An increase of these proinflammatory cytokines in the absence of any symptomatic manifestation of the inflammatory response can be considered as a possible tooth reparation parameter

Estimating the Effects of Dental Caries and Its Restorative Treatment on Periodontal Inflammatory and Oxidative Status: A Short Controlled Longitudinal Study

Dental caries and periodontitis are among the most common health conditions that are currently recognized as growing socio-economic problems relating to their increasing prevalence, negative socio-economic impact, and harmful effects on systemic health. So far, the exact effects of caries and standard restorative materials on periodontal inflammatory and oxidative status are not established. The present study aimed to investigate the effect of caries and its restoration using standard temporary and permanent filling materials on a panel of 16 inflammatory and oxidative markers in gingival crevicular fluid (GCF) of periodontally healthy individuals, 7 (D7) and 30 (D30) days post-restoration, while the intact teeth represented the control. One hundred ninety systemically and periodontally healthy patients with occlusal caries underwent standard cavity preparation and restorations with one of six standard temporary or permanent restorative material according to indication and randomization scheme. Interleukin (IL)-2, IFN- γ, IL-12, IL-17A, IL-13, IL-9, IL-10, IL-6, IL-5, IL-4, IL-22, TNF-α, IL1- β, thiobarbituric acid reactive substances, superoxide dismutase, and reduced form of glutathione were measured in GCF samples by flowcytometry and spectrophotometry in aid of commercial diagnostic assays. Caries affected teeth exhibited significantly increased IL-1 β, IL-17, IL-22, and TBARS and decreased IL-9 concentrations compared to healthy controls. Treatment generally resulted in an increased antioxidant capacity with exception of zinc-polycarboxylate cement showing distinctive inflammatory pattern. Comparison of inflammatory and oxidative profiles in temporary and permanent restorations showed material-specific patterning which was particularly expressed in temporary materials plausibly related to greater caries extension. Caries affected teeth exhibited a balanced inflammatory pattern in GCF, with a general tendency of homeostatic re-establishment following treatment. Restorative materials did not provide specific pathological effects, although some material groups did exhibit significantly elevated levels of inflammatory and oxidative markers compared to healthy controls, while the material-specific patterning was observed as well

Indoleamine 2,3-dioxygenase-dependent expansion of T-regulatory cells maintains mucosal healing in ulcerative colitis

© The Author(s), 2018. Background: Dendritic cell (DC)-derived indolamine 2,3-dioxygenase (IDO) degrades tryptophan to kynurenine, which promotes conversion of inflammatory T cells in immunosuppressive regulatory T cells (Tregs). We analyzed the significance of the IDO:Treg axis for inducing and maintaining mucosal healing in ulcerative colitis (UC). Methods: Dextran sodium sulphate (DSS)-induced colitis in BALB/c mice (model for mucosal healing) and C57BL/6 mice (model for persistent disease) was used. Serum, fecal samples and colon-infiltrating immune cells of 65 patients with UC with mucosal healing or persistent colitis were analyzed. Results: Significantly higher serum levels of kynurenine and downregulated inflammatory cytokines were noticed in DSS-treated BALB/c mice compared with C57BL/6 mice. Increased IDO activity and attenuated capacity for antigen presentation and production of inflammatory cytokines, observed in BALB/c DCs, was followed by a significantly lower number of inflammatory T helper 1 (Th1) and Th17 cells and a notably increased number of Tregs in the colons of DSS-treated BALB/c mice. DCs and Tregs were crucially important for the maintenance of mucosal healing since their depletion aggravated colitis. Mucosal healing, followed by an increase in kynurenine and intestinal Tregs, was re-established when BALB/c DCs were transferred into DC-depleted or Treg-depleted DSS-treated BALB/c mice. This phenomenon was completely abrogated by the IDO inhibitor. Significantly higher serum and fecal levels of kynurenine, accompanied by an increased presence of intestinal Tregs, were noticed in patients with UC with mucosal healing and negatively correlated with disease severity, fecal calprotectin, colon-infiltrating interferon γ and interleukin-17-producing cells, serum and fecal levels of inflammatory cytokines. Conclusion: IDO-dependent expansion of endogenous Tregs should be further explored as a new approach for the induction and maintenance of mucosal healing in patients with UC

Inflammatory Cytokines and Biodegradable Scaffolds in Dental Mesenchymal Stem Cells Priming

Mesenchymal stem cells (MSC) are multipotent stem cells with wide-ranging clinical applications due to their ability to regenerate tissue from mesenchymal origin and their capability of suppressing immune responses, thus reducing the likelihood of graft versus host disease after transplantation. MSCs can be isolated from a variety of sources including bone marrow, adipose tissue, umbilical cord blood, and immature teeth. Dental stem cells (DSC) possess progenitor and immunomodulatory abilities as the other MSC types and because they can be easily isolated, are considered as attractive therapeutic agents in regenerative dentistry. Recently, it has been shown that DSCs seeded onto newly developed synthetic biomaterial scaffolds have retained their potential for proliferation and at the same time have enhanced capabilities for differentiation and immunosuppression. The scaffolds are becoming more efficient at MSC priming as researchers learn how short peptide sequences alter the adhesive and proliferative capabilities of the scaffolds by stimulating or inhibiting classical osteogenic pathways. New findings on how to modulate the inflammatory microenvironment, which can prime DSCs for differentiation, combined with the use of next generation scaffolds may significantly improve their therapeutic potential. In this review, we summarize current findings regarding DSCs as a potential regenerative therapy, including stem cell priming with inflammatory cytokines, types of scaffolds currently being explored and the modulation of scaffolds to regulate immune response and promote growth