Scientists at Cincinnati Children’s generate functional stomach tissue in the lab and coax intestinal organoids to grow in mice

Someday, the mini-stomachs and mini-intestines grown at Cincinnati Children’s may pave the way for helping people with a wide range of digestive diseases grow their own replacement tissues.

But first, these organoid projects could advance lab research by providing sophisticated human organ models for use in drug development and basic developmental studies. Two recent papers demonstrate how quickly this technology is moving forward.

Stomachs from stem cells

A paper published Oct. 29 in Nature explains how scientists here managed to grow “gastric organoids” in the lab.

“Until this study, no one had generated gastric cells from human pluripotent stem cells (hPSCs),” says James Wells, PhD, principal investigator and a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children’s. “In addition, we discovered how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition.”

Initially, the pea-sized stomachs will help explore questions scientists could not probe with traditional technology. For example, the mini-stomachs will shed light on H. pylori bacterial infections, a major cause of peptic ulcer disease and stomach cancer. In addition, the techniques used to grow the stomach tissue may advance efforts to generate other organs that trace their roots to the foregut, such as the lungs and pancreas.

In addition to Wells, the research team included first author Kyle McCracken, an MD/PhD graduate student; and Yana Zavros, PhD, a researcher at the University of Cincinnati’s Department of Molecular and Cellular Physiology.

Read more about the stomach project. Wells also explains the project in a video.

Intestine organoids reach mature form in mice

Before the latest progress with stomach organoids, Wells and colleagues had reported similar successes in growing intestine tissue from iPSCs. Now that line of research has taken another important step.

A study published online Oct. 19 in Nature Medicine, details how researchers at Cincinnati Children’s successfully transplanted lab-grown organoids of human intestinal tissue into mice, where they grew into mature tissue. 

“This provides a new way to study the many diseases and conditions that can cause intestinal failure, from genetic disorders appearing at birth to conditions that strike later in life, such as cancer and Crohn’s disease,” says Michael Helmrath, MD, MS, lead investigator and surgical director of the Intestinal Rehabilitation Program at Cincinnati Children’s. “These studies also advance the longer-term goal of growing tissues that can replace damaged human intestine.”

Grafting the lab-grown organoids into the capsule of a mouse kidney provided the blood supply needed to help them grow into fully mature human intestinal tissue.

“The mucosal lining contains all the differentiated cells and continuously renews itself by proliferation of intestinal stem cells.  In addition, the mucosa develops both absorptive and digestive ability that was not evident in the culture dish,” Helmrath says. “Importantly, the muscle layers of the intestine also develop.”

Read more about the intestine project. Helmrath also explains the project in a video