Inflammatory Bowel Disease Drivers Revealed in Human Organ Chips

Overview

Journal medRxiv

Date 2024 Dec 16

PMID 39677416

Authors

Alican Ozkan

Gwenn Merry

David B Chou

Ryan R Posey

Anna Stejskalova

Karina Calderon

Megan Sperry

Viktor Horvath

Lorenzo E Ferri

Emanuela Carlotti

Stuart A C McDonald

Douglas J Winton

Rocco Riccardi

Lilianna Bordeianou

Sean Hall

Girija Goyal

Donald E Ingber

Affiliations

Soon will be listed here.

Abstract

Inflammatory bowel disease (IBD) patients exhibit compromised intestinal barrier function and decreased mucus accumulation, as well as increased inflammation, fibrosis, and cancer risk, with symptoms often being exacerbated in women during pregnancy. Here, we show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. Inflammation and fibrosis are accentuated by peristalsis-like motions in IBD Chips and when exposed to pregnancy-associated hormones in female IBD Chips. Carcinogen exposure also increases inflammation, gene mutations, and chromosome duplication in IBD Chips, but not in Healthy Chips. These data enabled by human Organ Chip technology suggest that the intestinal stroma and peristalsis-associated mechanical deformations play a key role in driving inflammation and disease progression in male and female IBD patients.

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