Differential Effects of Escherichia coli- Versus Porphyromonas gingivalis-derived Lipopolysaccharides on Dental Pulp Stem Cell Differentiation in Scaffold-free Engineered Tissues.
Differential Effects of Escherichia coli- Versus Porphyromonas gingivalis-derived Lipopolysaccharides on Dental Pulp Stem Cell Differentiation in Scaffold-free Engineered Tissues.
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DOI：
10.1016/j.joen.2022.08.010
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发表时间：
2022-11
影响因子：
4.2
通讯作者：
Syed-Picard, Fatima N.
中科院分区：
文献类型：
--
作者：
Rothermund, Kristi;Calabrese, Tia C.;Syed-Picard, Fatima N.
为了利用牙髓干细胞（DPSC）的治疗能力用于再生牙髓应用，需要更好地了解其先天防御和修复过程。脂多糖（LPS）是革兰阴性菌的主要致病因子，是引起牙髓感染的重要因素。我们已经开发了三维无支架DPSC组织，其自组织成牙本质牙髓类器官，其包括周边的矿化牙本质样组织和未矿化牙髓样核心。在这项研究中，无支架的DPSC构建体被用作可控的实验模型，以研究DPSC对细菌挑战的反应。使用从人第三磨牙分离的DPSC工程化无支架构建体。为了模拟细菌暴露，将DPSC构建体暴露于牙龈卟啉单胞菌衍生的LPS（牙龈卟啉单胞菌-LPS）或大肠杆菌衍生的LPS（大肠杆菌-LPS）。coli-LPS）。观察LPS对DPSC分化、增殖和凋亡的影响。缺乏LPS处理的工程组织自组织成牙本质牙髓类器官。LPS处理并没有负面影响DPSC的增殖或凋亡的工程组织。两个E. coli-LPS和P. gingivalis-LPS抑制RUNX 2 mRNA表达的上调，并降低成牙本质细胞相关蛋白的表达（p<0.05），表明LPS抑制成牙本质细胞分化。然而，只有E. coli-LPS处理显著减少DPSC构建体中的矿物质沉积（p<0.05），表明E. coli-LPS而非P. gingivalis-LPS可抑制DPSCs的功能分化，阻止DPSCs自组织形成牙本质牙髓复合体样结构。本研究建立了无支架DPSC构建口腔疾病模型。此外，它强调了来自不同细菌物种的LPS的多样性，并强调了在基础科学研究中利用来自临床相关细菌的LPS的必要性。
To leverage the therapeutic capabilities of dental pulp stem cells (DPSCs) for regenerative endodontic applications, a better understanding of their innate defense and reparative processes is needed. Lipopolysaccharide (LPS) is a major virulent factor of gram-negative bacteria and contributor to endodontic infections. We have developed three-dimensional scaffold-free DPSC tissues that self-organize into dentin-pulp organoids comprising a mineralized dentin-like tissue on the periphery and an unmineralized pulp-like core. In this study, scaffold-free DPSC constructs were utilized as controllable experimental models to study DPSC response to bacterial challenge. Scaffold-free constructs were engineered using DPSCs isolated from human third molars. To simulate bacterial exposure, DPSC constructs were exposed to either Porphyromonas gingivalis-derived LPS (P. gingivalis-LPS) or Escherichia coli-derived LPS (E. coli-LPS). The effects of LPS on DPSC differentiation, proliferation and apoptosis were evaluated. Engineered tissues lacking LPS treatment self-organized into dentin-pulp organoids. LPS treatment did not negatively affect DPSC proliferation or apoptosis in the engineered tissues. Both E. coli-LPS and P. gingivalis-LPS inhibited the upregulation of RUNX2 mRNA expression and reduced the expression of the odontoblast-associated proteins (p<0.05) suggesting that LPS is inhibiting odontoblastic differentiation. However, only E. coli-LPS treatment significantly reduced mineral deposition in the DPSC (p<0.05) constructs indicating that E. coli-LPS, but not P. gingivalis-LPS, reduced functional differentiation of DPSCs and prevented DPSCs from self-organizing into dentin-pulp complex-like structure. This study establishes scaffold-free DPSC constructs as models of oral disease. Furthermore, it emphasizes the diversity of LPS derived from different bacterial species and highlights the necessity of utilizing LPS derived from clinically relevant bacteria in basic science investigations.
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影响因子：
4.2
作者：
Kim, Jae-Hwan;Woo, Su-Mi;Jung, Ji-Yeon
通讯作者：
Jung, Ji-Yeon
影响因子：
7.6
作者：
Syed-Picard, F. N.;Ray, H. L., Jr.;Sfeir, C.
通讯作者：
Sfeir, C.
影响因子：
7.6
作者：
WARFVINGE, J;DAHLEN, G;BERGENHOLTZ, G
通讯作者：
BERGENHOLTZ, G
影响因子：
5
作者：
Widbiller, M.;Eidt, A.;Galler, K. M.
通讯作者：
Galler, K. M.
影响因子：
7.6
作者：
Botero, T. M.;Son, J. S.;Noer, J. E.
通讯作者：
Noer, J. E.