In collaboration with researchers at the University of Cincinnati College of Medicine, they used laboratory generated mini-stomachs (called gastric organoids) to study infection by H pylori bacteria, a major cause of peptic ulcer disease and stomach cancer.
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, according to Jim Wells, principal investigator and a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children's.
It also is the first time researchers have produced 3D human embryonic foregut - a promising starting point for generating other foregut organ tissues like the lungs and pancreas, he said.
"Until this study, no one had generated gastric cells from human pluripotent stem cells (hPSCs)," Wells said.
"In addition, we discovered how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition," he said.
This is important because differences between species in the embryonic development and architecture of the adult stomach make mouse models less than optimal for studying human stomach development and disease, Wells added.
The key to growing human gastric organoids was to identify the steps involved in normal stomach formation during embryonic development. By manipulating these normal processes in a petri dish, the scientists were able to coax pluripotent stem cells toward becoming stomach.
Over the course of a month, these steps resulted in the formation of 3D human gastric organoids that were about 3mm (1/10th of an inch) in diameter.
Writing in a journal, the researchers said they were impressed by how rapidly H pylori bacteria infected stomach epithelial tissues.
Within 24 hours, the bacteria had triggered biochemical changes to the organ.
The human gastric organoids faithfully mimicked the early stages of gastric disease caused by the bacteria, including the activation of a cancer gene called c-Met and the rapid spread of infection in epithelial tissues, researchers said.