Objective Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model.
Design Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air–liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma.
Results The resulting ‘mucosoid cultures’, so named because they recapitulate key characteristics of the gastric mucosa, represent normal stem cell-driven cultures that can be passaged for months. These highly polarised columnar epithelial layers encompass the various gastric antral cell types and secrete mucus at the apical surface. By default, they differentiate towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates proliferation of MUC6-producing cells and preserves stemness—reminiscent of the gland base. Stromal cells from the lamina propria secrete Wnt inhibitors, antagonising stem-cell niche signalling and inducing differentiation. On infection with H. pylori, a strong inflammatory response is induced preferentially in the undifferentiated basal cell phenotype. Infection of cultures for several weeks produces foci of viable bacteria and a persistent inflammatory condition, while the secreted mucus establishes a barrier that only few bacteria manage to overcome.
Conclusion Gastric mucosoid cultures faithfully reproduce the features of normal human gastric epithelium, enabling new approaches for investigating the interaction of H. pylori with the epithelial surface and the cross-talk with the basolateral stromal compartment. Our observations provide striking insights in the regulatory circuits of inflammation and defence.
- mucosoid cultures
- human stomach
- columnar epithelium
- stromal cells
- mucus secretion
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Contributor FB: study design, experimental design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, statistical analysis. SW, AI-M and PM: experimental design, acquisition of data, and analysis and interpretation of data. GS: acquisition of data. CG: electron microscopy. HB: bioinformatics support, statistical analysis. MS: mass spectrometry. CD and JO: provision of materials. TFM: study concept and design, critical revision of the manuscript, obtained funding and study supervision.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Ethics committee of the Charité University Medicine, Berlin (EA1/129/12).
Provenance and peer review Not commissioned; externally peer reviewed.
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