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Peer-reviewedCC BY 4.0Cells

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

5 affiliations
  1. 1Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 16635-148, Iran
  2. 2Department of Internal Medicine, Metabolic Diseases and Angiology, Faculty of Health Sciences in Katowice, Medical University of Silesia in Katowice, 40-635 Katowice, Poland
  3. 3Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran 16635-148, Iran
  4. 4Department of Developmental Biology, School of Basic Sciences and Advanced Technologies in Biology, University of Science and Culture, Tehran 13145-871, Iran
  5. 5Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 16635-148, Iran

Abstract

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.

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BibTeX
@article{najafabadi2026modeling,
  title = {{Modeling the Human Stomach In Vitro: Gastric Organoids in Development, Disease, and Therapy}},
  author = {Zahra Enteshari Najafabadi and Ireneusz Ryszkiel and Hossein Baharvand and Amir Sadeghi and Agata Stanek and Anna Meyfour},
  journal = {Cells},
  year = {2026},
  month = oct,
  doi = {10.3390/cells15211973},
  url = {https://www.mdpi.com/2073-4409/15/21/1973},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Modeling the Human Stomach In Vitro: Gastric Organoids in Development, Disease, and Therapy
AU  - Zahra Enteshari Najafabadi
AU  - Ireneusz Ryszkiel
AU  - Hossein Baharvand
AU  - Amir Sadeghi
AU  - Agata Stanek
AU  - Anna Meyfour
PY  - 2026
DA  - 2026/10/29
JO  - Cells
DO  - 10.3390/cells15211973
UR  - https://www.mdpi.com/2073-4409/15/21/1973
AB  - 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.
SN  - 2073-4409
ER  -