Disease models

Fundus organoids derived from human pluripotent stem cells could be used to screen therapies for peptic ulcers and other gastric diseases. The organoids were generated by culturing human pluripotent stem cells in a cocktail of wingless-type MMTV integration site family member 3A (WNT3A), fibroblast growth factor 4 (FGF4), retinoic acid, other growth factors and antagonists, to induce differentiation into foregut progenitor cells. The progenitors were treated with a glycogen synthase kinase 3β (GSK3B) inhibitor to activate β-catenin (CTNNB1) to induce development into 3-D organoids that contained chief and parietal cells specific to the fundus. In organoids treated with histamine to induce stomach acid production, famotidine and omeprazole decreased acid levels as measured by pH compared with no treatment. Next steps include testing mice implanted with the organoids as models of gastric disease.

The generic histamine H2 receptor (HRH2; H2R) inhibitor famotidine is marketed for peptic ulcers and gastroesophageal reflux disease (GERD)...