Lay Summary

Proposal No.  IBD-0114
Principal Investigator:  Ewa Carrier, M.D.
Applicant Organization:  University of California, San Diego (La Jolla, U.S.A.)
Project Title:  Repair of Crohn’s disease with stem cells
Period of Award:  September 1, 2004 – September 30, 2007

The primary objective of this work is to establish an animal model for the treatment of Crohn’s disease with stem cells.  We are a part of a clinical protocol in humans on high dose chemotherapy and stem cell transplantation for Crohn’s disease and observed a significant improvement in clinical symptoms in these patients within a year post transplant.  The mechanism for this improvement is unknown.

This proposal will develop a relevant animal model and study the effects of stem cells (embryonic and adult) on the immune recovery and regeneration of epithelium in the intestine of mice with colitis following stem cell injection.  In the process of developing colitis, the immune balance in the intestine is distorted and the shift from tolerant to immune state occurs.  In order for repair to occur, this process has to be reversed and new cells implanted to generate a “new” immune system.  This is an “immune reset” that will lead to symptomatic improvement.  In fact, this was shown to be the case in transplants related to other autoimmune diseases, such as lupus erythematosus and scleroderma.

We have developed an animal model of colitis in IL10 knock out mice using piroxicam.  The colitis in the piroxicam-induced mice will not improve unless rescue therapy is provided.  Therefore, the mice will have progressive symptoms and die unless effective therapy is implemented.  We will use these mice to study how stem cells (embryonic and adult) can affect this outcome and what is the biological model of this repair.  Therefore, at the conclusion of these studies, we will have developed a viable model of stem cell therapy in Crohn’s disease and utilize the knowledge developed by this research for the development of new clinical protocols.