Celiac disease patient derived iPSC–small intestinal epithelial cells are more persistent under cytokine stimuli than healthy control cells

Abstract Background & Aims Celiac disease is a wheat-induced immune-mediated enteropathy. Intestinal organoid models for adult stem cell–based celiac disease exist, but planar intestinal models derived from celiac disease patients that would allow direct assessment from both sides of the epithelium have been lacking. We aimed to bridge this gap by setting up a two-dimensional in vitro model based on small intestinal epithelial cells (SIECs) derived from induced pluripotent stem cells (iPSC) from celiac disease patients. Methods IPSCs from celiac disease and control patients were sequentially differentiated towards SIECs. The model’s applicability was tested under cytokine stimuli. Results Celiac disease and control patient iPSCs matured similarly towards SIECs. However, they had inherent gene expression differences in inflammation- and immune-related genes, such as IRF1 and HLA-DRB1. Both iPSC-SIECs responded in a SIEC-specific manner to the cytokine stimulation. The response in celiac disease iPSC-SIECs was attenuated compared with that of control iPSC-SIECs. Conclusions The data confirm that iPSC-derived SIECs represent an appropriate platform for studying inflammation-associated enteropathies, such as celiac disease, but also suggest that there might be inherent patient-specific or cell type–specific differences in the responses.