Unexpected cause of inflammatory bowel disease identified

Inflammatory bowel diseases — Crohn's disease and ulcerative colitis — affect millions of people worldwide, yet the mechanism of their development remains incompletely understood. Neither cell cultures nor animal models have been able to reproduce the disease sufficiently well. A new study published in Nature Biomedical Engineering (NBE) proposes the first comprehensive model of both diseases.

Bioengineer Alican Ozkan from Harvard University, together with colleagues, created a "Colon Chip" — a microfluidic device populated with cells from patients with Crohn's disease and ulcerative colitis. The chip reproduces not only the cellular environment of the intestine but also the mechanical stretching of walls during peristalsis.

The key finding turned out to be unexpected. Fibroblasts — connective tissue cells that were considered passive "scaffolding" of organs — behaved as active participants in inflammation. When healthy epithelial cells were placed on the chip alongside fibroblasts from patients with the disease, the healthy cells began behaving as if they were diseased: the intestinal barrier weakened and inflammatory markers increased. Fibroblasts alone, without other components of the inflamed environment, proved to be a sufficient trigger.

The chip also made it possible to reproduce flare-ups in pregnant women with inflammatory bowel diseases — for the first time in laboratory conditions. Additionally, the model showed that fibroblasts from diseased patients enhance oncogenic changes upon exposure to carcinogens. The authors plan to use the platform to search for new therapeutic targets and to test drugs on human cells.