Peer-reviewedCC BY-NC-NDNature Biomedical Engineering
Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects
13 affiliations
- 1AbbVie Bioresearch Center, Worcester, MA, USA
- 2Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA
- 3Department of Pathology, Massachusetts General Hospital, Boston, MA, USA
- 4Entact Bio, Watertown, MA, USA
- 5Department of Experimental Surgery and Department of Surgery, McGill University, Montreal, Quebec, Canada
- 6Thoracic and Upper GI Cancer Research Laboratories, Research Institute of McGill University Health Centre, Montreal, Quebec, Canada
- 7Clonal Dynamics in Epithelia Laboratory, Queen Mary University of London, London, UK
- 8Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK
- 9Department of Surgery, Massachusetts General Hospital, Boston, MA, USA
- 10Iovance Therapeutics, Tampa, FL, USA
- 11Harvard John A. Paulson School of Engineering and Applied Sciences, Boston, MA, USA. [email protected]
- 12Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. [email protected]
- 13Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA. [email protected]
Abstract
Inflammatory bowel disease (IBD) patients 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 show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. Inflammation and fibrosis are accentuated by peristalsis-like motions in IBD Chips and when exposed to pregnancy-associated hormones in female IBD Chips. Carcinogen exposure also increases inflammation, gene mutations, and chromosome duplication in IBD Chips, but not in Healthy Chips. These data enabled by human Organ Chip technology suggest that the intestinal stroma, sex hormones, and peristalsis-associated mechanical deformations play a key role in driving inflammation, fibrosis, and disease progression in male and female IBD patients.
Related
- Serum proteins predict incident inflammatory bowel disease 14 years before diagnosis: a machine-learning and Cox modelling in the UK Biobank
- Disentangling Context-Specific Alzheimer's Disease Progression Signatures through an Explainable AI Framework
- Identification of Transcriptional Hippo Response Signature Connecting Inflammatory Bowel Disease and Colorectal Cancer Progression
- Disease-specific C-reactive protein heterogeneity across common infections is associated with a shared systemic inflammatory laboratory profile
- Control of muscle timing with respect to specific muscles is established and compiled just prior to response initiation
BibTeX
@article{ozkan2026human,
title = {{Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects}},
author = {Aliçan Özkan and Gwenn E. Merry and David Benson Chou and Ryan R. Posey and Anna Stejskalová and Karina Calderon and Megan M. Sperry and Joshua Piatok and Viktor Horvath and Lorenzo E. Ferri and Emanuela Carlotti and Stuart A.C. McDonald and Douglas J. Winton and Rocco Ricciardi and Liliana Bordeianou and Sean Hall and Girija Goyal and Donald E. Ingber},
journal = {Nature Biomedical Engineering},
year = {2026},
month = may,
doi = {10.1038/s41551-026-01686-8},
url = {https://doi.org/10.1038/s41551-026-01686-8},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Human inflammatory bowel disease-on-a-chip for modelling disease progression, cancer initiation and sex-specific effects
AU - Aliçan Özkan
AU - Gwenn E. Merry
AU - David Benson Chou
AU - Ryan R. Posey
AU - Anna Stejskalová
AU - Karina Calderon
AU - Megan M. Sperry
AU - Joshua Piatok
AU - Viktor Horvath
AU - Lorenzo E. Ferri
AU - Emanuela Carlotti
AU - Stuart A.C. McDonald
AU - Douglas J. Winton
AU - Rocco Ricciardi
AU - Liliana Bordeianou
AU - Sean Hall
AU - Girija Goyal
AU - Donald E. Ingber
PY - 2026
DA - 2026/05/21
JO - Nature Biomedical Engineering
DO - 10.1038/s41551-026-01686-8
UR - https://doi.org/10.1038/s41551-026-01686-8
AB - Inflammatory bowel disease (IBD) patients 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 show that these IBD hallmarks can be replicated using human Organ Chips lined by IBD patient-derived colon epithelial cells interfaced with matched fibroblasts cultured under flow. Use of heterotypic tissue recombinants revealed that IBD fibroblasts are the primary drivers of multiple IBD symptoms. Inflammation and fibrosis are accentuated by peristalsis-like motions in IBD Chips and when exposed to pregnancy-associated hormones in female IBD Chips. Carcinogen exposure also increases inflammation, gene mutations, and chromosome duplication in IBD Chips, but not in Healthy Chips. These data enabled by human Organ Chip technology suggest that the intestinal stroma, sex hormones, and peristalsis-associated mechanical deformations play a key role in driving inflammation, fibrosis, and disease progression in male and female IBD patients.
SN - 2157-846X
ER -