BOSTON – A series of important technological advances in cloning stem cells of the gastrointestinal tract is rewriting the basic concepts surrounding these cells and has the potential to advance understanding of GI conditions such as Barrett’s esophagus and Crohn’s disease, according to the winner of the 2016 AGA-Medtronic Research and Development Pilot Award in Technology.

The award is sponsored by Medtronic and administered through the AGA Research Foundation. “Medtronic is pleased to partner with the AGA Research Foundation in supporting research to improve patient outcomes,” said Vafa Jamali, president of Early Technologies’ business with Medtronic. “We are dedicated to support patient-friendly innovations enabling the early detection and treatment of chronic GI diseases and cancers.”

From left, Dr. Michael L. Kochman, Dr. Wa Xian, Dr. Bani Chander-Roland, and Vafa Jamali.

Award winner Wa Xian, PhD, gave an update on her research at the 2017 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.

“The enabling technology we developed is the means of cloning and propagating single mucosal stem cells from discrete regions of the gastrointestinal tract in their most immature form. What we have shown is that these stem cells from normal individuals are essentially immortal, are genetically stable, and, critically, are rigorously regiospecific,” Dr. Xian of the Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center, Houston, said in an interview.

“This regiospecificity – duodenum stem cells always yield duodenum epithelia, ascending colon stem cells produce ascending colon epithelia – has important implications for both regenerative medicine and drug discovery,” she added.

With regard to the dominant stem cell technologies in use today, including induced pluripotent stem cells and organoid cultures of the gastrointestinal tract, Dr. Xian’s technology represents a paradigm shift.

Dr. Xian’s system generates pure “ground state” stem cells that differentiate in 3-D culture to an epithelium indistinguishable from textbook images of in situ epithelia, at rates 250 times faster than intestinal organoid systems.

This system is being applied in major investigations into Barrett’s esophagus and inflammatory bowel disease in collaboration with investigators at multiple centers in the United States and Singapore.

For Barrett’s, Dr. Xian has developed patient-matched stem cells from endoscopic biopsies of esophageal, Barrett’s, and gastric cardia to show that each arises from distinct lineages, and that the Barrett’s stem cells accumulate genetic alterations not found in those of the matched normal epithelia. These stem cells have been adapted to a drug-screening platform to identify leads that specifically eliminate Barrett’s with an eye on preemptive therapies.

Her work on mucosal stem cells in patients with Crohn’s and ulcerative colitis is revealing a coexistence of normal and pathogenic stem cells in these patients that may alter concepts of both the etiology and treatment of these conditions.

Dr. Xian suggests that treatment of Crohn’s may become analogous to treatment of cancer – emphasizing preservation of healthy cells while eliminating diseased cells – and move therapy from the current effort to induce a quiescent inflammatory state to one in which the goal is cure.

“These findings appear to indicate that some of the chronic inflammatory conditions so prevalent in gastroenterology, as well as the cancers arising from them, may have as their basis profound alterations in mucosal stem cell biology,” she added.

Though it’s still early days with this technology, its single-cell resolution naturally melds with other emerging genomic and genome editing technologies into a powerful means of dissecting the molecular basis of disease and realizing the potential of autologous regenerative medicine, according to Dr. Xian.

Following Dr. Xian’s presentation, Michael L. Kochman, MD, who is executive committee chair of the AGA Center for GI Innovation and Technology, announced the winner of the 2017 AGA-Medtronic Research and Development Pilot Award in Technology. The award was presented to Bani Chander Roland, MD, of Lenox Hill Hospital & Northwell Health System, New York. Her research will involve assessment of the ileocecal valve.

“She has several aims in this proposal to really understand better the causes of ileosphincter dysfunction using a novel method of measuring ileocecal junction pressures,” reported Dr. Kochman. He explained that other parts of the proposal included ileocecal evaluation with wireless capsule endoscopy as well as an evaluation of flora across the GI tract.

A new award to foster innovation in GI medtech is also planned. In partnership with Boston Scientific, the AGA has established the AGA-Boston Scientific Technology and Innovation Pilot Award. This $30,000 research grant will support investigators at any career stage who are developing and testing new medical devices and technologies with applications in gastroenterology and hepatology. The details of the award will be available on the AGA’s website in May. Applications for the award will be accepted beginning in the fall.

VIDEO: Awardee's work targets mucosal stem cells in Crohn’s, ulcerative colitis