Human gastric multi-regional assembloids for functional parietal maturation and patient-specific modelling of antral foveolar hyperplasia

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Authors list

Brendan C Jones Giada Benedetti Giuseppe Calà Ramin Amiri Lucinda Tullie Roberto Lutman Jahangir Sufi Lucy Holland Daniyal J Jafree Monika Balys Glenn Anderson Ian C Simcock Owen J Arthurs Simon Eaton Nicola Elvassore Vivian Li Christopher J Tape Kelsey DJ Jones Camilla Luni Giovanni Giuseppe Giobbe Paolo De Coppi
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Abstract

Patient-derived human organoids have the capacity to self-organize into more complex structures. However, to what extent gastric organoids can recapitulate differentiated cell types and mucosal functions remains unexplored. Here we report on how region-specific gastric organoids can self-assemble into complex multi-regional assembloids. These assembloids show increased complexity and cross-communication between different gastric regions, allowing for the emergence of the elusive parietal cell type that is responsible for the production of gastric acid and shows a functional response to drugs targeting the H+/K+ ATPase pump. We generate assembloids from paediatric patients with a genetic condition found to be associated with unusual antral foveolar hyperplasia and hyperplastic polyposis. Our multi-regional assembloid efficiently recapitulates hyperplastic-like antral regions, with decreased mucin secretion and glycosylated H+/K+ ATPase subunit beta, which results in impaired gastric acid secretion. Multi-regional gastric assembloids, generated using paediatric-stem-cell-derived organoids, successfully recapitulate the structural and functional characteristics of the human stomach, offering a promising tool for studying gastric epithelial interactions and disease mechanisms that were previously challenging to investigate in primary models.

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Journal Nature Biomedical Engineering
Pages Epub ahead of print
Available online
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Publisher website (DOI) 10.1038/s41551-025-01553-y
Europe PubMed Central 41578032
Pubmed 41578032

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