Scientific Abstract

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

 

Intestinal homeostasis is maintained by the robust activity of intestinal stem cells (ISC) which allow complete regeneration of the intestinal epithelium every five to seven days. Inflammatory bowel disease (IBD) is a disabling disorder of the intestine in which inflammation leads to intestinal destruction with secondary infection, bleeding, malnutrition, and associated events such as autoimmune disease and cancer. Despite the remarkable regenerative potential of ISCs, considerable barriers to the use of ISCs for regenerative therapy of inflammatory bowel disease (IBD) have included lack of robust ISC markers, and the inability to culture and/or expand ISCs ex vivo. Accordingly, we have devised culture systems able to support growth and multi-lineage differentiation of colon epithelium for > 100 days, which furthermore recapitulate the Wnt- and Notch-dependency of the colon in vivo. Further, we have successfully developed FACS-based strategies to purify ISCs from intestine using recently described markers. In the current application, we will merge these methodologies towards the purification, characterization, ex vivo expansion, and administration of ISC towards stem cell-based therapies of IBD.