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

Abstract 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.