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Related Experiment Video

Updated: May 15, 2025

Author Spotlight: Studying the Epithelial Effects of Intestinal Inflammation In Vitro on Established Murine Colonoids
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Published on: June 2, 2023

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Inflamed Intestinal Epithelial Cells From Patients With Ulcerative Colitis Restore a Noninflamed Transcriptional

Alexander Due Hammerhøj1, Theresa Louise Boye1, Jiayi Yao2

  • 1Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.

Laboratory Investigation; a Journal of Technical Methods and Pathology
|April 10, 2025
PubMed
Summary

Intestinal stem cells from ulcerative colitis patients lose their inflammatory signature when cultured in vitro. This suggests expanded cells could be used for therapeutic transplantation to promote intestinal healing in ulcerative colitis patients.

Keywords:
RNA sequencingcellular memoryintestinal stem cellsorganoid morphologyprednisoloneulcerative colitis

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Area of Science:

  • Gastroenterology
  • Stem Cell Biology
  • Inflammatory Bowel Disease Research

Background:

  • Ulcerative colitis (UC) involves chronic inflammation of the colon, with intestinal stem cells (ISCs) from inflamed tissue showing an inflammatory gene profile.
  • A key question is whether these ISCs retain inflammatory memory after isolation and expansion.

Purpose of the Study:

  • To investigate if human intestinal epithelial cells maintain an in vivo inflammatory state when cultured as 3D organoids in vitro.
  • To assess the suitability of these expanded cells for therapeutic transplantation in UC.

Main Methods:

  • ISCs were isolated from non-IBD controls and UC patients (glucocorticoid-naïve and prednisolone-treated).
  • Epithelial cells were cultured as 3D intestinal organoids and harvested at passage 2 for bulk RNA sequencing.
  • Organoid morphology was analyzed in relation to the tissue's inflammatory state.

Main Results:

  • In vitro-cultured epithelial cells from inflamed UC tissue did not retain the hallmarks of inflammation observed in vivo.
  • A correlation was found between organoid morphology and the tissue of origin's inflammatory status, with inflamed colon-derived organoids showing reduced circularity.

Conclusions:

  • Expanded ISCs may be suitable for autologous transplantation to promote intestinal healing in active UC.
  • Further clinical studies are warranted to explore the therapeutic potential of these cells.