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<p>Patients affected by inflammatory bowel disease (IBD) 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 replicate these IBD hallmarks in human-derived organ-on-a-chip devices lined by colon epithelial cells from individuals with IBD when interfaced with matched fibroblasts, cultured under flow, exposed to peristalsis-like motions and perfused with circulating immune cells. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. In the IBD chip, inflammation and fibrosis are accentuated by peristalsis-like motions and, in female-derived chips, also by exposure to pregnancy-associated hormones. When exposed to carcinogens, the IBD chip shows increased inflammation, gene mutations and chromosome duplication, in contrast to healthy chips. These data suggest that the intestinal stroma, sex hormones and peristalsis-associated mechanical deformations have a key role in driving inflammation, fibrosis and disease progression in male and female individuals with IBD.</p>

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Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月21日

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  • Alican Özkan,
  • Gwenn E. Merry,
  • David B. Chou,
  • Ryan R. Posey,
  • Anna Stejskalova,
  • Karina Calderon,
  • Megan Sperry,
  • Joshua Piatok,
  • Viktor Horvath,
  • Lorenzo E. Ferri,
  • Emanuela Carlotti,
  • Stuart A. C. McDonald,
  • Douglas J. Winton,
  • Rocco Ricciardi,
  • Liliana Bordeianou,
  • Sean Hall,
  • Girija Goyal,
  • Donald E. Ingber

摘要

Patients affected by inflammatory bowel disease (IBD) 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 replicate these IBD hallmarks in human-derived organ-on-a-chip devices lined by colon epithelial cells from individuals with IBD when interfaced with matched fibroblasts, cultured under flow, exposed to peristalsis-like motions and perfused with circulating immune cells. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. In the IBD chip, inflammation and fibrosis are accentuated by peristalsis-like motions and, in female-derived chips, also by exposure to pregnancy-associated hormones. When exposed to carcinogens, the IBD chip shows increased inflammation, gene mutations and chromosome duplication, in contrast to healthy chips. These data suggest that the intestinal stroma, sex hormones and peristalsis-associated mechanical deformations have a key role in driving inflammation, fibrosis and disease progression in male and female individuals with IBD.