Lay Summary

Proposal No. IBD-0237R

Principal Investigator: Calvin Kuo, M.D., Ph.D.

Applicant Organization: Stanford University (California, U.S.A.)

Project Title: Intestinal stem cells for therapy of inflammatory bowel diseases

Period of Award: September 1, 2008 – August 31, 2010

 

Current therapy of inflammatory bowel disease (IBD) focuses on modulation of the immune response and associated inflammation that are primary mediators of intestinal damage. On the other hand, it could be desirable to also enhance the healing of the intestine in IBD, thereby accelerating repair of the intestinal lining. Here, we propose to use intestinal stem cells (ISC) as a method to enhance intestinal regeneration for therapy of IBD. Unfortunately, while it has long been known that ISCs are responsible for the ability to regenerate its lining every five to seven days, the proper tools to harness ISCs for IBD therapy have not previously been available. In response, we have recently developed novel methods to allow growth of the intestine in culture for more than 100 days. Further, we have devised methods to allow purification of ISCs from colon taking advantage of proteins selectively expressed on the ISC surface. In the current studies, these tools will be combined to allow human ISCs to be isolated, expanded in culture outside of the body, and then re-administered into mice with IBD-like illnesses to test possible regenerative and ameliorating effects of the ISCs as they incorporate into the diseased intestine. These approaches would be a first step towards applying the regenerative potential of ISCs to treat IBD and its devastating complications.