Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection

Boccellato, Francesco; Woelffling, Sarah; Imai-Matsushima, Aki; Sánchez, Gabriela; Goosmann, Christian; Schmid, Monika S.; Berger, Hilmar; Morey, Pau; Denecke, Christian; Ordemann, J.; Meyer, Thomas F.

doi:10.1136/gutjnl-2017-314540

Cited by 88 publications

(122 citation statements)

References 41 publications

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“…Expression of MUC6, a pyloric gland cell marker, was absent in differentiated gastroid monolayers, but was weakly positive in undifferentiated gastroid monolayers (Figure E,F). HGM45 and MUC5AC are the same gastric epithelial and mucin markers, and some previous studies showed that the expression of MUC5AC and MUC6 depended on Wnt3A and RSPO1 . Those studies also mention that withdrawing Wnt‐3A and RSPO1 changed undifferentiated gastroid monolayers (deep basal mucosa) to differentiated ones (gastric surface mucosa).…”

Section: Resultsmentioning

confidence: 88%

“…Schlaermann et al described that gastric spheroids constituted an undifferentiated stage and it was possible to differentiate differentiated one by withdrawing Wnt3A and RSPO1. Using their methods, we studied both undifferentiated (with Wnt3A and RSPO1) and differentiated (withdrawal of Wnt3A and RSPO1) gastroid monolayers.…”

Section: Resultsmentioning

confidence: 99%

“…In Figure B, we show that the TEER rapidly recovered even with TN2GF4 wild‐type infection consistent with the notion that the apical junctional complex of gastroid monolayers is robust and confirming that the TEER of gastroid monolayers was not altered by these virulence factors. The TEER range differs depending on the cell type; the maximum TEER reported has been 470 Ω cm 2 on mucosoid vs, 80‐1400 Ω cm 2 on conventional cell lines . Studies with conventional cell lines showed that TEER approximately dropped 30%‐50% permanently compared with base levels during 8‐48 hours co‐culture with H pylori .…”

Section: Discussionmentioning

confidence: 99%

“…Also in our study, H pylori specifically attached to areas of mucous area as seen by TEM (Figure C,D). A study using gastric mucosa which is an ex vivo model like our gastroid monolayers, Boccellato et al reported the surface of the mucus was a barrier against infection. Mucous production is another feature of this model that is similar to in vivo conditions; conversely, cancer cell lines used for H pylori experiments, such as AGS cells, lack mucous expression …”

Section: Discussionmentioning

confidence: 99%

“…In contrast, 2D cultures are physiologic and infection with H pylori is both simple and reliable. Previous studies have suggested that 2D polarized monolayers derived from human stomach are a suitable ex vivo model for H pylori infection …”

Section: Introductionmentioning

confidence: 99%

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Changes of tight junction and interleukin‐8 expression using a human gastroid monolayer model of Helicobacter pylori infection

et al. 2019

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Background Lack of a model that mirrors Helicobacter pylori‐induced gastric mucosal inflammation has hampered investigation of early host‐bacterial interactions. We used an ex vivo model of human stomach, gastric epithelial organoid monolayers (gastroid monolayers) to investigate interactions of H pylori infection and the apical junctional complex and interleukin‐8 (IL‐8) expression. Method Morphology of human antral mucosal gastroid monolayers was evaluated using histology, immunohistochemical (IHC) staining, and transmission electron microscopy (TEM). Functional and gross changes in the apical junctional complexes were assessed using transepithelial electrical resistance (TEER), cytotoxicity assays, and confocal laser scanning microscopy. IL‐8 expression was evaluated by real‐time quantitative PCR and ELISA. Results When evaluated by IHC and TEM, the morphology of gastroid monolayers closely resembled in vivo human stomach. Following inoculation of H pylori, TEER transiently declined (up to 51%) in an H pylori density‐dependent manner. TEER recovered by 48 hours post‐infection and remained normal despite continued presence and replication of H pylori. Confocal scanning microscopy showed minimal disruption of zonula occludens‐1 or E‐cadherin structure. IL‐8 production was unchanged by infection with either CagA‐positive or CagA‐negative H pylori and JNK and MEK inhibitors did not suppress IL‐8 production, whereas p38 and IKK inhibitor significantly did. Conclusion Human gastroid monolayers provide a model for experimental H pylori infection more consistent with in vivo human infections than seen with typical gastric epithelial cell lines. This ex vivo system should lead to better understanding of H pylori host‐pathogen interactions.

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Section: Resultsmentioning

confidence: 88%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes of tight junction and interleukin‐8 expression using a human gastroid monolayer model of Helicobacter pylori infection

et al. 2019

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Organoid‐Based Human Stomach Micro‐Physiological System to Recapitulate the Dynamic Mucosal Defense Mechanism

et al. 2023

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Several stomach diseases are attributed to the dysregulation of physiological function of gastric mucosal barrier by pathogens. Gastric organoids are a promising tool to develop treatment strategies for gastric infections. However, their functional features of in vivo gastric mucosal barrier and host–microbe interactions are limited due to the lack of physiological stimuli. Herein, a human stomach micro‐physiological system (hsMPS) with physiologically relevant gastric mucosal defense system is described based on the combination of organoid and MPS technology. A fluid flow enhanced epithelial‐mesenchymal interaction in the hsMPS enables functional maturation of gastric epithelial cells, which allows for the recreation of mesh‐like mucus layer containing high level of mucus protective peptides and well‐developed epithelial junctional complexes. Furthermore, gastroprotection mechanisms against Helicobacter pylori (H. pylori) are successfully demonstrated in this system. Therefore, hsMPS represents a new in vitro tool for research where gastric mucosal defense mechanism is pivotal for developing therapeutic strategies.

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Microphysiological Constructs and Systems: Biofabrication Tactics, Biomimetic Evaluation Approaches, and Biomedical Applications

Zhang,

Xu,

et al. 2023

Small Methods

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In recent decades, microphysiological constructs and systems (MPCs and MPSs) have undergone significant development, ranging from self‐organized organoids to high‐throughput organ‐on‐a‐chip platforms. Advances in biomaterials, bioinks, 3D bioprinting, micro/nanofabrication, and sensor technologies have contributed to diverse and innovative biofabrication tactics. MPCs and MPSs, particularly tissue chips relevant to absorption, distribution, metabolism, excretion, and toxicity, have demonstrated potential as precise, efficient, and economical alternatives to animal models for drug discovery and personalized medicine. However, current approaches mainly focus on the in vitro recapitulation of the human anatomical structure and physiological‐biochemical indices at a single or a few simple levels. This review highlights the recent remarkable progress in MPC and MPS models and their applications. The challenges that must be addressed to assess the reliability, quantify the techniques, and utilize the fidelity of the models are also discussed.

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Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection

Cited by 88 publications

References 41 publications

Changes of tight junction and interleukin‐8 expression using a human gastroid monolayer model of Helicobacter pylori infection

Changes of tight junction and interleukin‐8 expression using a human gastroid monolayer model of Helicobacter pylori infection

Organoid‐Based Human Stomach Micro‐Physiological System to Recapitulate the Dynamic Mucosal Defense Mechanism

Microphysiological Constructs and Systems: Biofabrication Tactics, Biomimetic Evaluation Approaches, and Biomedical Applications

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