We have made substantial progress in our study and have completed all 5 Aims. We successfully obtained biopsy-derived cells and blood samples from pediatric-onset Crohn’s disease patients that had a history of intestinal fibrosis. We reprogrammed the blood samples to iPSCs, directed them to form mini-guts and subsequently purified the mesenchymal cell component. We were then able to successfully use these cells for high-throughput screening of antifibrotic agents. We identified one such compound that abrogated the fibrotic response, and confirmed that it also attenuated the response in the biopsy-derived cell counterparts. More in-depth analysis revealed that similar fibrosis-related proteins were secreted in both biopsy-derived and iPSC-derived cells. All in all, this confirms the iPSC-derived approach of utilizing a patient’s mini-guts for high throughput screening of antifibrotic agents, and thus removes a major bottleneck in the field of intestinal fibrosis.