Modeling the Human Stomach In Vitro: Gastric Organoids in Development, Disease, and Therapy

Gastric organoids are advanced three-dimensional models generated from adult or pluripotent stem cells. By reproducing key structural, cellular, and functional features of gastric tissue, they overcome several limitations of conventional two-dimensional cultures and animal models. Gastric organoids provide physiologically relevant platforms for studying stomach development, cellular differentiation, and the molecular mechanisms underlying gastric diseases. This review summarizes the principal cell sources and protocols used to generate gastric organoids and discusses recent advances in culture systems, including two-dimensional organoid-derived monolayers, air–liquid interface cultures, co-culture systems, and organoid-on-a-chip technologies. Particular attention is given to the application of gastric organoids in modeling Helicobacter pylori infection, SARS-CoV-2 infection, and gastric cancer, as well as in evaluating therapeutic responses. Their roles in developmental biology, the investigation of congenital disorders, drug screening, potential precision-medicine application, biobanking, and regenerative medicine are also discussed. Despite their considerable potential, current gastric organoid models remain limited: conventional epithelial organoids lack stromal, immune, neural, and vascular components; PSC-derived organoids contain only a limited mesenchymal population; and more complex engineered multicellular tissues still depend largely on in vivo engraftment for maturation. Variable maturation, dependence on poorly defined extracellular matrices, and insufficient standardization further limit their translation.