Stem Cell-Generated Stomach Organoids to Boost Gastric Disease Research

Research on gastric diseases will benefit from the development of complex organoid structures containing functional stomach fundic epithelium tissue that were generated from human pluripotent stem cells.

Despite the global prevalence of gastric disease, there are few adequate models in which to study the fundus epithelium of the human stomach. To fill this gap, investigators at Cincinnati Children's Hospital Medical Center differentiated human pluripotent stem cells (hPSCs) into gastric organoids containing fundic epithelium by first identifying and then recapitulating key events in embryonic fundus development.

The investigators reported in the January 4, 2017, online edition of the journal Nature that disruption of Wnt/beta-catenin signaling in mouse embryos led to conversion of fundic to antral epithelium, and that beta-catenin activation in hPSC-derived foregut progenitors promoted the development of human fundic-type gastric organoids (hFGOs). The investigators then used hFGOs to identify temporally distinct roles for multiple signaling pathways in epithelial morphogenesis and differentiation of fundic cell types, including chief cells and functional parietal cells.

"Now that we can grow both antral- and corpus/fundic-type human gastric mini-organs, it is possible to study how these human gastric tissues interact physiologically, respond differently to infection, injury and react to pharmacologic treatments," said senior author Dr. James M. Wells, director of the pluripotent stem cell facility at Cincinnati Children's Hospital Medical Center. "Diseases of the stomach impact millions of people in the United States and gastric cancer is the third leading cause of cancer-related deaths worldwide."