Scientists grow mini stomachs to model disease through the directed differentiation of human pluripotent stem cells

Written by Alexandra Thompson

Researchers from Cincinnati Children’s Hospital Medical Center in Ohio have grown a fully functioning, miniature human stomach using pluripotent stem cells

James M Wells (departments of Developmental Biology and Endocrinology, Cincinnati Children’s Hospital Medical Center) and colleagues yesterday published research in Nature demonstrating the use of human pluripotent stem cells (hPSCs) to grow gastric organoids — a miniature human stomach.

“Until this study, no one had generated gastric cells from hPSCs,” says Wells, principal investigator of the study. “In addition, we discovered how to promote formation of 3D gastric tissue with complex architecture and cellular composition.”

The team began by researching the embryonic development of the stomach, in order to try and replicate these processes (emporal manipulation of the FGF, WNT, BMP, retinoic acid and EGF signaling pathways and 3D growth) with hPSCs in vitro.

The organoids had primitive gastric gland- and pit-like domains, proliferative zones containing LGR5-expressing cells, surface and antral mucous cells, and a diversity of gastric endocrine cells. As good animal models for the stomach are lacking, and as these organoids represented the human stomach well, the researchers used the organoids as a model to study the pathogenesis of H. pylori infection.

Earlier this month, the Cincinnati Children’s Hospital Medical Center team published research on their development of fully functioning, miniature human intestines from iPSCs. They successfully transplanted these miniature intestines into the kidneys of mice.

Clearly, this team is doing some fantastic work developing models for the development and pathogenesis of the digestive system, and hopefully this research could one day lead to the development personalized tissue or organs that can be transplanted into patients.

Sources: McCracken KW, EM Catá, Crawford CM et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature doi:10.1038/nature13863 (2014) (Epub ahead of print); Medical News Today: