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Updated: Oct 9, 2025

Combining Human Organoids and Organ-on-a-Chip Technology to Model Intestinal Region-Specific Functionality
Published on: May 5, 2022
The Progress of Intestinal Epithelial Models from Cell Lines to Gut-On-Chip
Shafaque Rahman1, Mohammed Ghiboub1,2, Joanne M Donkers3
1Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The Netherlands.
Preclinical models for studying intestinal diseases like inflammatory bowel disease (IBD) often fail to replicate the complex human gut environment. This review explores advanced in vitro and ex vivo models for better translational research.
Area of Science:
- Gastroenterology
- Translational Medicine
- Biomedical Engineering
Background:
- Preclinical in vitro and ex vivo models have advanced understanding of intestinal functions and diseases like inflammatory bowel disease (IBD).
- However, these models often struggle to fully replicate the complex multifactorial in vivo human gut environment, including microbiota, nutrition, and immune responses.
- This limitation hinders the translation of findings from preclinical studies to human clinical applications.
Purpose of the Study:
- To review and synthesize recent advancements in in vitro and ex vivo intestinal models.
- To discuss the setup, advantages, and limitations of various models used for studying intestinal physiology and disease.
- To provide future perspectives on the development and application of these models in health and disease research.
Main Methods:
- Review of current literature on in vitro and ex vivo intestinal models.
- Analysis of established and emerging models including cell lines, Ussing chambers, everted sacs, organoids, InTESTine™, and microfluidic gut-on-chip systems.
- Comparative assessment of model capabilities in reflecting in vivo human gut conditions.
Main Results:
- Conventional models (cell lines, Ussing chamber, everted sac) are still utilized but have limitations in mimicking the in vivo environment.
- Sophisticated models like organoids, InTESTine™, and gut-on-chip systems offer improved recapitulation of gut complexity.
- Each model presents unique advantages and limitations regarding setup, cost, and biological relevance.
Conclusions:
- Advanced in vitro and ex vivo models are crucial for overcoming the translational gap in intestinal research.
- Organoids and gut-on-chip technologies show significant promise for studying intestinal physiology and diseases like IBD.
- Further development and validation of these sophisticated models are essential for accurate prediction of human gut responses.

