Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Inflammatory bowel disease (IBD) is characterized by chronic inflammation in the intestines. Due to the limited progress in achieving a radical treatment for IBD, there is an urgent need to develop effective drugs. However, it is difficult for current colonic epithelial models to accurately recapitulate the IBD pathophysiology because those models do not contain stromal cells. Here, we tried to establish an IBD model using human ES/iPS cell-derived colon organoids (COs), consisting of intestinal epithelial and stromal cells. Then, we attempt to apply this model in the development of drugs for IBD. COs were treated with TNF-α, IFN-γ, and IL-1β (3 cytokines: 3CK) to replicate the IBD pathophysiology. We found that stromal cells in COs mainly produced various inflammatory cytokines in response to 3CK treatment, while intestinal epithelial cells, which express cytokine receptors, exhibited a loss of their distinctive characteristics. The gene expression profile of 3CK-treated COs was similar to that of the colon of patients with ulcerative colitis. These results suggested that 3CK-treated COs recapitulate the IBD pathophysiology. We then investigated whether our IBD model is useful for evaluating the efficacy of IBD drugs. The treatment of tofacitinib, an approved drug for IBD, ameliorated the IBD-related phenotypes in 3CK-treated COs, including the inflammatory cytokines secretion or epithelial dysfunctions, suggesting the potential usefulness of 3CK-treated COs in IBD drug development. We anticipate that our IBD model accelerate the development of effective and safe drugs.
