title: Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens.
abstract: 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-1β, 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.
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore; Institute of Medical Biology, Agency for Science, Technology and Research (ASTAR), Singapore.
authors.forename: Gopu
authors.identifier: 0000-0001-8423-5197
authors.initials: G
authors.lastname: Sriram
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Vaishali Prakash
authors.identifier: 0000-0002-0658-6183
authors.initials: VP
authors.lastname: Natu
authors.affiliation: Discipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Intekhab
authors.identifier: 0000-0002-7754-0609
authors.initials: I
authors.lastname: Islam
authors.affiliation: Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Xin
authors.identifier: 0000-0001-9726-9388
authors.initials: X
authors.lastname: Fu
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Chaminda Jayampath
authors.initials: CJ
authors.lastname: Seneviratne
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore.
authors.forename: Kai Soo
authors.identifier: 0000-0002-9865-9828
authors.initials: KS
authors.lastname: Tan
authors.affiliation: Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, Singapore; Tissue Engineering Program, Life Sciences Institute, National University of Singapore, Singapore.
authors.forename: Tong
authors.identifier: 0000-0002-7994-9627
authors.initials: T
authors.lastname: Cao