Scientists Develop Model for IBD Fibrosis Using Stem Cells

Intestinal fibrosis is a serious complication of Crohn's disease. Over time, parts of the bowel can scar and narrow, which can significantly degrade digestion. Nearly a third of patients with this form of inflammatory bowel disease (IBD) will develop this debilitating complication and require surgery. Despite improvements in the treatment and management of Crohn’s, there are no therapeutics that can prevent or reverse the excessive accumulation of scar tissue in the intestinal wall.

"A major challenge to the study of intestinal fibrosis is that cells of this condition can only be obtained through invasive procedures such as colonoscopy or surgical resection, and they have a very limited lifespan outside of the body. This greatly impairs research into the mechanisms underpinning this condition as well as potential therapeutics," said Robert Barrett, PhD, an assistant professor of Medicine at Cedars-Sinai and co-principal investigator of the study.

"Now, all we need is a simple blood draw to generate stem cells that can be directed to form near-unlimited quantities of cells for the study of intestinal fibrosis."

The 3D human intestinal structures, called organoids, are grown from induced pluripotent stem cells and contain two types of cells implicated in the development of fibrosis: intestinal epithelial and mesenchymal cells. Purified populations of both cell types can then be obtained from the mini-intestines and treated with chemical messengers that induce fibrosis.

"In addition to the advantage of being able to now produce a robust and continuous cell model system for biological research, there is a personalized medicine aspect of this new approach," said Stephan R. Targan, MD, co-principal investigator of the study, director of the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai, and the Feintech Family Chair in Inflammatory Bowel Disease. "These cells are specific to the individuals from whom they were derived, so we may now be able to identify mechanisms underpinning intestinal fibrosis in a patient specific manner."

Barrett says researchers also plan to use micro-engineered chip technology to incorporate both cell types to better assess how cell-to-cell interactions may influence the process of thickening and scarring.

"We want to identify the novel mechanisms underpinning intestinal fibrosis that could be amenable to therapeutic intervention," said Barrett. "The ultimate goal, of course, is to find new ways to decrease or eliminate the fibrotic response in Crohn’s patients and the need for hospitalizations and surgeries."

Funding: Research reported in this study was funded by the Crohn’s and Colitis Foundation, the Board of Governors Regenerative Medicine Institute, Barbara Herman, and the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute.