Establishment of an ulcerative colitis model using colon organoids derived from human induced pluripotent stem cells.

Abstract

The etiology of inflammatory bowel disease (IBD) is complex, with much room for a greater understanding and development of improved therapies. Therefore, establishing a reliable IBD model is crucial for future advancements. In this study, human induced pluripotent stem (iPS) cell-derived colon organoids (hiPSC-COs) were treated with a combination of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin (IL)-1β (3 cytokines [3CK]), known to be elevated in the serum of IBD patients. Inflammatory responses in stromal cells and damage to intestinal epithelial cells were observed in the 3CK-treated hiPSC-COs. Comparison of molecular signatures of 3CK-treated hiPSC-COs with those of ulcerative colitis (UC) patient's colon revealed that 3CK-treated hiPSC-COs resemble UC patient's colon. Furthermore, the elevated production of inflammatory cytokines observed in 3CK-treated hiPSC-COs was attenuated by treatment with tofacitinib. Our UC model will be an essential tool to understand its pathologic mechanisms and identify effective therapeutic approaches.