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      Mechanical force modulates inflammation and immunomodulation in periodontal ligament cells

      research-article
      , , , ,
      Medical Review
      De Gruyter
      mechanical stimuli, periodontal ligament, immunomodulation, inflammation, periodontal ligament stem cell

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          Abstract

          Mechanical forces control a multitude of biological responses in various cells and tissues. The periodontal ligament, located between the tooth’s root and alveolar bone, is a major tissue compartment that is incessantly subjected to such mechanical stimulation through either normal or abnormal oral functionality. It is now known that mechanical stimulation activates periodontal ligament stem cells (PDLSCs) to modulate periodontal immunity and regulate inflammation – a basic feature of periodontal disease that affects virtually every human during their lifetime. For instance, shear stress induces the expression of immunomodulatory-related gene, indoleamine 2,3-dioxygenase (IDO). IDO cleaves l-tryptophan, resulting in increased l-kynurenine levels that, in turn, further promote regulatory T-cell differentiation and inhibit T cell proliferation. These and other related data reinforce the notion that mechanical stimulation plays a crucial role in controlling inflammation and immunomodulation of periodontal tissues. Further investigations, however, are warranted to evaluate the immunomodulatory features of PDLSCs so as to understand the pathological basis of periodontal disease and translate these into clinical interventions.

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          Most cited references16

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          Discovery of IDO1 Inhibitors: From Bench to Bedside

          Small molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1) are emerging at the vanguard of experimental agents in oncology. Here pioneers of this new drug class provide a bench-to-bedside review on preclinical validation of IDO1 as a cancer therapeutic target and on the discovery and development of a set of mechanistically distinct compounds – indoximod, epacadostat and navoximod – that were first to be evaluated as IDO inhibitors in clinical trials. As ‘immunometabolic adjuvants’ to widen therapeutic windows, IDO inhibitors may leverage not only immuno-oncology modalities but also chemotherapy and radiotherapy as standards of care in the oncology clinic.
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            Immunomodulatory properties of human periodontal ligament stem cells.

            Tissue engineering utilizing periodontal ligament stem cells (PDLSCs) has recently been proposed for the development of new periodontal regenerative therapies. Although the use of autologous PDLSC transplantation eliminates the potential of a significant host immune response against the donor cells, it is often difficult to generate enough PDLSCs from one donor source due to the variation of stem cell potential between donors and disease state of each patient. In this study, we examined the immunomodulatory properties of PDLSCs as candidates for new allogeneic stem cell-based therapies. Human PDLSCs displayed cell surface marker characteristics and differentiation potential similar to bone marrow stromal stem cells (BMSSCs) and dental pulp stem cells (DPSCs). PDLSCs, BMSSCs, and DPSCs inhibited peripheral blood mononuclear cell (PBMNC) proliferation stimulated with mitogen or in an allogeneic mixed lymphocyte reaction (MLR). Interestingly, gingival fibroblasts (GFs) also suppressed allogeneic PBMNC proliferation under both assay conditions. PDLSCs, BMSSCs, DPSCs, and GFs exhibited non-cell contact dependent suppression of PBMNC proliferation in co-cultures using transwells. Furthermore, conditioned media (CM) derived from each cell type pretreated with IFN-gamma partially suppressed PBMNC proliferation when compared to CMs without IFN-gamma stimulation. In all of these mesenchymal cell types cultured with activated PBMNCs, the expression of TGF-beta1, hepatocyte growth factor (HGF) and indoleamine 2, 3-dioxygenase (IDO) was upregulated while IDO expression was upregulated following stimulation with IFN-gamma. These results suggest that PDLSCs, BMSSCs, DPSCs, and GFs possess immunosuppressive properties mediated, in part, by soluble factors, produced by activated PBMNCs. J. Cell. Physiol. 219: 667-676, 2009. (c) 2009 Wiley-Liss, Inc.
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              Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress

              Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibroblast-like cells that can differentiate into cells of multiple lineages, such as chondrocytes, osteoblasts, adipocytes, myoblasts, and others. These multipotent MSCs can be found in nearly all tissues but mostly located in perivascular niches, playing a significant role in tissue repair and regeneration. Additionally, MSCs interact with immune cells both in innate and adaptive immune systems, modulating immune responses and enabling immunosuppression and tolerance induction. Understanding the biology of MSCs and their roles in clinical treatment is crucial for developing MSC-based cellular therapy for a variety of pathological conditions. Here, we review the progress in the study on the mechanisms underlying the immunomodulatory and regenerative effects of MSCs; update the medical translation of MSCs, focusing on the registration trials leading to regulatory approvals; and discuss how to improve therapeutic efficacy and safety of MSC applications for future.
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                Author and article information

                Contributors
                Journal
                Med Rev (2021)
                Med Rev (2021)
                mr
                mr
                Medical Review
                De Gruyter
                2097-0773
                2749-9642
                13 August 2024
                December 2024
                : 4
                : 6
                : 544-548
                Affiliations
                deptFaculty of Dentistry, Center of Excellence for Dental Stem Cell Biology , universityChulalongkorn University , Bangkok, Thailand
                deptDivision of Molecular and Regenerative Prosthodontics , universityTohoku University Graduate School of Dentistry , Sendai, Miyagi, Japan
                deptCenter for Advanced Stem Cell and Regenerative Research , universityTohoku University Graduate School of Dentistry , Sendai, Miyagi, Japan
                deptDean Office and Office of Research Affairs, Faculty of Dentistry , universityChulalongkorn University , Bangkok, Thailand
                deptFaculty of Dentistry , universityThe University of Hong Kong , Hong Kong Special Administrative Region, China
                deptDepartment of Anatomy, Faculty of Dentistry , universityChulalongkorn University , Bangkok, Thailand
                Author notes
                Corresponding author: Thanaphum Osathanon, deptFaculty of Dentistry, Center of Excellence for Dental Stem Cell Biology , universityChulalongkorn University , Bangkok 10700, Thailand; and deptDepartment of Anatomy, Faculty of Dentistry , universityChulalongkorn University , Bangkok 10700, Thailand, E-mail: thanaphum.o@ 123456chula.ac.th
                Author information
                https://orcid.org/0000-0003-1649-6357
                Article
                mr-2024-0034
                10.1515/mr-2024-0034
                11629306
                39664083
                397fcc61-55aa-43fc-b745-afeb96496cff
                © 2024 the author(s), published by De Gruyter, Berlin/Boston

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 10 April 2024
                : 31 July 2024
                Page count
                Figures: 02, Tables: 00, References: 16, Pages: 05
                Funding
                Funded by: Second Century (C2) high potential professoriate fund
                Funded by: Ratchadapiset Somphot Fund for Postdoctoral Fellowship
                Funded by: The NSRF via the Program Management Unit for Human Resources & Institutional Development, Research and Innovation
                Award ID: B16F640118
                Categories
                Perspective

                mechanical stimuli,periodontal ligament,immunomodulation,inflammation,periodontal ligament stem cell

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