Researchers from U.S. generated functional, three-dimensional human stomach tissue to create miniature stomachs using pluripotent stem cells in a laboratory. Stomach development is strikingly similar between human and mice. A mouse gut, shown here, confirmed that the lab-grown human stomachs were growing the right way. “Pretty much everything that the mouse stomach was doing during development, our [stomach] organoids were also doing,” said researcher Jim Wells, a professor of developmental biology at Cincinnati Children’s Hospital Medical Center. “And that told us we were accurately reproducing the normal stages of stomach development.”
Human pluripotent stem cells can transform into any cell type in the body. The tiny stomachs are the first grown from pluripotent human stem cells. They form complex, 3D structures. To make them, the researchers used both basic research and trial and error until they found the right chemical switches to turn on and off during development. “Until this study, no one had generated gastric cells from human pluripotent stem cells (hPSCs),” said Jim Wells, principal investigator and a scientist at Cincinnati Children’s Hospital Medical Center.
“In addition, we discovered how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition,” Wells added. “This first-time molecular generation of 3D human gastric organoids (hGOs) presents new opportunities for drug discovery, modelling early stages of stomach cancer and studying some of the underpinnings of obesity related diabetes,” Wells said. By manipulating these normal processes in a petri dish, the scientists were able to coax pluripotent stem cells into becoming stomach cells.
Over the course of a month, these steps resulted in the formation of 3D human gastric organoids that were about 3 mm in diameter. The study appeared in the journal Nature. The organoids are not complete stomachs, the researchers said. The tissue is a model for the gastric antrum, the part of the stomach that makes proteins that direct functions such as digestive enzyme production. The researchers are now studying ways to make the part of the stomach responsible for acid production.