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      Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens

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          Periodontitis involves complex interplay of bacteria and host immune response resulting in destruction of supporting tissues of the tooth. Toll-like receptors (TLRs) play a role in recognizing microbial pathogens and eliciting an innate immune response. Recently, the potential application of multipotent stem cells and pluripotent stem cells including human embryonic stem cells (hESCs) in periodontal regenerative therapy has been proposed. However, little is known about the impact of periodontopathogens on hESC-derived progenies. This study investigates the effects of heat-killed periodontopathogens, namely, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, on TLR and cytokine expression profile of hESC-derived progenies, namely, fibroblasts (hESC-Fib) and mesenchymal stem cells (hESC-MSCs). Additionally, the serotype-dependent effect of A. actinomycetemcomitans on hESC-derived progenies was explored. Both hESC-Fib and hESC-MSCs constitutively expressed TLR-2 and TLR-4. hESC-Fib upon exposure to periodontopathogens displayed upregulation of TLRs and release of cytokines (IL-1 β, IL-6, and IL-8). In contrast, hESC-MSCs were largely nonresponsive to bacterial challenge, especially in terms of cytokine production. Further, exposure of hESC-Fib to A. actinomycetemcomitans serotype c was associated with higher IL-8 production than serotype b. In contrast, the hESC-MSCs displayed no serotype-dependent response. Differential response of the two hESC progenies implies a phenotype-dependent response to periodontopathogens and supports the concept of immunomodulatory properties of MSCs.

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          Most cited references 64

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              Embryonic Stem Cell Lines Derived from Human Blastocysts


                Author and article information

                Stem Cells Int
                Stem Cells Int
                Stem Cells International
                Hindawi Publishing Corporation
                25 August 2016
                : 2016
                1Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore
                2Institute of Medical Biology, Agency for Science, Technology and Research (A *STAR), Singapore
                3Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore
                4Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China
                5NUS Graduate School for Integrative Sciences and Engineering, Singapore
                6Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore
                Author notes

                Academic Editor: Zhaohui Ye

                Copyright © 2016 Gopu Sriram et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: National University Health System Research
                Award ID: R221000085733
                Funded by: NUS Research Scholarship and President Graduate Fellowship
                Research Article

                Molecular medicine


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