The human stomach contains a complex, three-dimensional (3D) glandular epithelium organized into two different functional domains: the fundus (corpus), which is the major source of acid and peptidases, and the antrum (pylorus) that comprises of mucus secreting cells and endocrine cells. Gastric diseases, including peptic ulcer disease and gastric cancer, affect 10% of the world's population. Nevertheless, the cellular biology of the stomach is still poorly understood compared to other gastrointestinal organs, such as the liver, intestine, and colon. In particular, little is known about the molecular basis of gastric development and gastric lineage differentiation. Although animal models can be used to study the development, function and disease of the stomach, the species differences in embryonic development and architecture of the adult stomach make these animal models suboptimal for studying human gastric organogenesis and pathogenesis. In order to look at gastric development, function, and disease in a human context, a model system of the human stomach is imperative.
Human gastric organoids (HGOs) derived from primary stomach tissue start from isolated glands or single gland cells. Both isolated glands and single cells can give rise to gastric organoids, which can stay as cell types within the gastric gland or change lineages and become cell types of the gastric pit by manipulating Wnt signaling. These organoids contain only gastric epithelium and may require different matrix properties than gastric organoids derived from human pluripotent stem cells (hPSCs), which possess both mesenchyme and epithelium. HGOs can be used for a variety of purposes, including genetic modeling, drug screening, and possibly even in future patient transplantation. In addition, HGOs are very suitable for studying the development and interaction of non-epithelial cell types, such as endothelial cells, neuronal cells, and mesenchymal cells, which have hardly been studied.
OrganoLab's mission is to develop reliable, consistent models of the organs involved in digestion, especially models of the esophagus, stomach, intestine and pancreas. Our scientists have devised a method that allows cells from the gastric corpus/fundus region to be grown in the laboratory. These miniature organs can aid research into common gastrointestinal diseases and improve drug research.
References
- McCracken K. W. et al.; Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature, 2014, 516(7531): 400-404.
- Eicher A. K. et al.; Translating Developmental Principles to Generate Human Gastric Organoids. Cell Mol Gastroenterol Hepatol. 2018, 5(3): 353-363.
- Dye, B. R. et al.; Take a deep breath and digest the material: organoids and biomaterials of the respiratory and digestive systems. MRS Communications, 2017, 7(3): 502-514.
- Pompaiah M. et al.; Gastric Organoids: An Emerging Model System to Study Helicobacter pylori Pathogenesis. Curr Top Microbiol Immunol. 2017, 400: 149-168.
- Broda T. R. et al.; Generation of human antral and fundic gastric organoids from pluripotent stem cells. Nat Protoc. 2019, 14(1): 28-50.
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