Re-inducing inflammation in organoids from UC patients

Patient-derived intestinal organoids provide a powerful tool to better understand mechanisms underlying inflammatory bowel disease (IBD), but patient-specific organoids quickly lose their inflammatory phenotype. A Belgian group showed that inflammation can efficiently be (re-)induced in organoids from ulcerative colitis (UC) patients as well as non-IBD individuals [1].

First author Kaline Arnauts (Catholic University of Leuven, Belgium) explained the hypothesis that in order to study UC in an ex vivo model, inflammation should be re-induced towards levels corresponding to the in vivo situation. The researchers also wanted to know if organoids derived from inflamed regions are relatively sensitive to inflammatory stimulation. They therefore obtained biopsies from 8 patients with active UC, both from inflamed and non-inflamed regions, and from 8 non-IBD controls.

Exposure to the inflammatory mix induced transcriptional activation of inflammatory genes (including CXCL1, DUOXA2, IL1β, IL8, and IL23α; all P<0.001) and pathways in all conditions. Organoids of non-IBD controls clustered separate from organoids of UC patients. However, Arnauts added that organoids from inflamed and non-inflamed regions in UC patients were indistinguishable, also after inflammatory stimulation. She concluded: “To study UC in an ex vivo model, inflammation should be re-introduced prior to evaluation of other mechanisms. It is, however, not essential for organoid cultures to be obtained from biopsies from inflamed regions in UC patients.”

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   1. Arnauts K, et al. ECCO-IBD 2020, OP11.

Posted on 14 April 20208 April 2024