ArticleCellular and molecular gastroenterology and hepatology2021
A Novel Microphysiological Colon Platform to Decipher Mechanisms Driving Human Intestinal Permeability.
Article in Cellular and molecular gastroenterology and hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Human colon organoid Transwell model for investigating epithelial growth and repair.npj biomedical innovations · 2026Article
- Enhancements of symbiotic adhesion and antibiotic efficacy observed by the metabolic crosstalk within cell-bacteria cocultured on a microfluidic gut chip.Journal of pharmaceutical analysis · 2026Article
- Application of 3D Cell Culture Techniques in Nanotoxicology: How Far Are We?Stem cell reviews and reports · 2026Review
- Advanced human organoid-on-chip with physiological cellular complexity reveals bidirectional secretion patterns.iScience · 2026Article
- A Century of Progress Toward Gut Barrier Targeting Therapies in Inflammatory Diseases.The American journal of pathology · 2025Article
- Microfluidic Systems to Mimic the Blood-Brain Barrier: from Market to Engineering Challenges and Perspectives.ACS biomaterials science & engineering · 2025Review
- Cancer-on-a-chip for precision cancer medicine.Lab on a chip · 2025Review
- State-of-the-art in high throughput organ-on-chip for biotechnology and pharmaceuticals.Clinical and experimental reproductive medicine · 2025Article
- Advancing intestinal disease research using gut-on-a-chip.Regenerative therapy · 2025Review
- Ion transport and epithelial barrier dysfunction in experimental models of ulcerative colitis.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- High-throughput assay for predicting diarrhea risk using a 2D human intestinal stem cell-derived model.Toxicology in vitro : an international journal published in association with BIBRA · 2025Article
- Patient-derived esophageal adenocarcinoma organ chip: a physiologically relevant platform for functional precision oncology.Journal of translational medicine · 2025Article
- Leveraging Organ-on-Chip Models to Investigate Host-Microbiota Dynamics and Targeted Therapies for Inflammatory Bowel Disease.Advanced healthcare materials · 2025Review
- Review
- Intestinal organ chips for disease modelling and personalized medicine.Nature reviews. Gastroenterology & hepatology · 2024Review
- Cultivating complexity: Advancements in establishing in vitro models for the mucus-adhering gut microbiota.Microbial biotechnology · 2024Review
- High-Throughput Assay for Predicting Diarrhea Risk Using a 2D Human Intestinal Stem Cell-Derived Model.bioRxiv : the preprint server for biology · 2024Article
- Establishment and evaluation of on-chip intestinal barrier biosystems based on microfluidic techniques.Materials today. Bio · 2024Review
- Current applications of intestinal organoids: a review.Stem cell research & therapy · 2024Review
- A Pillar/Perfusion Plate Enhances Cell Growth, Reproducibility, Throughput, and User Friendliness in Dynamic 3D Cell Culture.ACS biomaterials science & engineering · 2024Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 4 countries.
Funding
Abstract
BACKGROUND &
aimsThe limited availability of organoid systems that mimic the molecular signatures and architecture of human intestinal epithelium has been an impediment to allowing them to be harnessed for the development of therapeutics as well as physiological insights. We developed a microphysiological Organ-on-Chip (Emulate, Inc, Boston, MA) platform designed to mimic properties of human intestinal epithelium leading to insights into barrier integrity.
methodsWe combined the human biopsy-derived leucine-rich repeat-containing G-protein-coupled receptor 5-positive organoids and Organ-on-Chip technologies to establish a micro-engineered human Colon Intestine-Chip (Emulate, Inc, Boston, MA). We characterized the proximity of the model to human tissue and organoids maintained in suspension by RNA sequencing analysis, and their differentiation to intestinal epithelial cells on the Colon Intestine-Chip under variable conditions. Furthermore, organoids from different donors were evaluated to understand variability in the system. Our system was applied to understanding the epithelial barrier and characterizing mechanisms driving the cytokine-induced barrier disruption.
resultsOur data highlight the importance of the endothelium and the in vivo tissue-relevant dynamic microenvironment in the Colon Intestine-Chip in the establishment of a tight monolayer of differentiated, polarized, organoid-derived intestinal epithelial cells. We confirmed the effect of interferon-γ on the colonic barrier and identified reorganization of apical junctional complexes, and induction of apoptosis in the intestinal epithelial cells as mediating mechanisms. We show that in the human Colon Intestine-Chip exposure to interleukin 22 induces disruption of the barrier, unlike its described protective role in experimental colitis in mice.
conclusionsWe developed a human Colon Intestine-Chip platform and showed its value in the characterization of the mechanism of action of interleukin 22 in the human epithelial barrier. This system can be used to elucidate, in a time- and challenge-dependent manner, the mechanism driving the development of leaky gut in human beings and to identify associated biomarkers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.