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<p>Disruption of the intestinal epithelial barrier is a hallmark of Inflammatory Bowel Disease (IBD), yet mechanisms of epithelial repair remain poorly understood. We developed a scalable human colon organoid-derived model in a 96-well Transwell system that recapitulates the cellular diversity and barrier function of the native epithelium. Using this platform, we investigated how various growth factors and cytokines influence epithelial maturation and repair following simulated inflammatory damage. Our results demonstrate that restorative factors, particularly EGF and TGFα, significantly enhance barrier integrity by reducing cell death and supporting proliferation under both chronic and acute inflammatory conditions. We also showed direct protective effects of immunomodulatory cytokines IL-2 and IL-10 on epithelial cells. This robust model provides a powerful high-throughput tool for dissecting mechanisms of intestinal repair and screening potential therapeutics to promote mucosal healing in IBD.</p>

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Human colon organoid Transwell model for investigating epithelial growth and repair

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月2日

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  • Xinming Tong,
  • Loryn Holokai,
  • Mary Keir,
  • Mercedesz Balazs,
  • Jing Li

摘要

Disruption of the intestinal epithelial barrier is a hallmark of Inflammatory Bowel Disease (IBD), yet mechanisms of epithelial repair remain poorly understood. We developed a scalable human colon organoid-derived model in a 96-well Transwell system that recapitulates the cellular diversity and barrier function of the native epithelium. Using this platform, we investigated how various growth factors and cytokines influence epithelial maturation and repair following simulated inflammatory damage. Our results demonstrate that restorative factors, particularly EGF and TGFα, significantly enhance barrier integrity by reducing cell death and supporting proliferation under both chronic and acute inflammatory conditions. We also showed direct protective effects of immunomodulatory cytokines IL-2 and IL-10 on epithelial cells. This robust model provides a powerful high-throughput tool for dissecting mechanisms of intestinal repair and screening potential therapeutics to promote mucosal healing in IBD.