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

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 multipo...

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Main Authors: Gopu Sriram, Vaishali Prakash Natu, Intekhab Islam, Xin Fu, Chaminda Jayampath Seneviratne, Kai Soo Tan, Tong Cao
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2016/8905365
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author Gopu Sriram
Vaishali Prakash Natu
Intekhab Islam
Xin Fu
Chaminda Jayampath Seneviratne
Kai Soo Tan
Tong Cao
author_facet Gopu Sriram
Vaishali Prakash Natu
Intekhab Islam
Xin Fu
Chaminda Jayampath Seneviratne
Kai Soo Tan
Tong Cao
author_sort Gopu Sriram
collection DOAJ
description 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.
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spelling doaj-art-70a55243bde9482ca94a6f41fe9964d52025-02-03T01:01:51ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/89053658905365Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to PeriodontopathogensGopu Sriram0Vaishali Prakash Natu1Intekhab Islam2Xin Fu3Chaminda Jayampath Seneviratne4Kai Soo Tan5Tong Cao6Discipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, SingaporeDiscipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, SingaporeDiscipline of Oral and Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore, SingaporeResearch Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDiscipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, SingaporeDiscipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, SingaporeDiscipline of Oral Sciences, Faculty of Dentistry, National University of Singapore, SingaporePeriodontitis 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.http://dx.doi.org/10.1155/2016/8905365
spellingShingle Gopu Sriram
Vaishali Prakash Natu
Intekhab Islam
Xin Fu
Chaminda Jayampath Seneviratne
Kai Soo Tan
Tong Cao
Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens
Stem Cells International
title Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens
title_full Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens
title_fullStr Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens
title_full_unstemmed Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens
title_short Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens
title_sort innate immune response of human embryonic stem cell derived fibroblasts and mesenchymal stem cells to periodontopathogens
url http://dx.doi.org/10.1155/2016/8905365
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