Tissue-engineered stomach opens doors to new research

Tissue-engineered human stomach tissues from the corpus/fundus region, which produce acid and digestive enzymes. Image: Cincinnati Children's Hospital

Using pluripotent stem cells, Cincinnati Children’s Hospital researchers have grown human stomach tissues that secrete acid and digestive enzymes in a petri dish. Now, researchers may grow tissue from this region of the stomach to better understand stomach development and disease.

The team, led by Jim Wells, director of the Pluripotent Stem Cell Facility at Cincinnati Children’s, generated tissues from the stomach’s corpus and fundus regions and previously engineered the antrum, the part of the stomach that produces hormones, according to a statement.

“Now that we can grow both antral- and corpus/fundic-type human gastric mini-organs, it’s possible to study how these human gastric tissues interact physiologically, respond differently to infection, injury and react to pharmacologic treatments,” Wells said in the statement.

Wells’ lab studies the way organs form during embryonic development and is interested in landing on new treatments for genetic forms of diseases, such as monogenic diabetes. Before engineering stomach tissue in a lab dish, they had to first determine how the stomach forms in the embryo, Wells said.

They found that the genetic pathway WNT/β-catenin helps regulate the development of the corpus/fundus stomach region in mouse embryos. The team applied this knowledge to human pluripotent stem cells to form human fundus organoids. They then honed the process, pinpointing other signaling pathways that give rise to various stomach cell types that occur in the fundus, such as those that secrete the enzyme pepsin and those that produce hydrochloric acid.

Next up, Wells’ team will transplant the tissue-generated stomach organoids into mice and see how they fare in modeling human gastric diseases.

In particular, Wells and colleague Yana Zavros want to gauge the organoids’ response to H pylori infection. The bacterium causes chronic gastritis, stomach ulcers and is a risk factor for stomach cancer. Additionally, stomach organoids may be studied in tandem with intestinal organoids to shed light on conditions that affect the gastrointestinal tract.