Enhanced Utilization of Induced Pluripotent Stem Cell–Derived Human Intestinal Organoids Using Microengineered Chips
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Background and Aims Human intestinal organoids derived from induced pluripotent stem cells have tremendous potential to elucidate the intestinal epithelium's role in health and disease, but it is difficult to directly assay these complex structures. This study sought to make this technology more amenable for study by obtaining epithelial cells from induced pluripotent stem cell–derived human intestinal organoids and incorporating them into small microengineered Chips. We then investigated if these cells within the Chip were polarized, had the 4 major intestinal epithelial subtypes, and were biologically responsive to exogenous stimuli. Methods Epithelial cells were positively selected from human intestinal organoids and were incorporated into the Chip. The effect of continuous media flow was examined. Immunocytochemistry and in situ hybridization were used to demonstrate that the epithelial cells were polarized and possessed the major intestinal epithelial subtypes. To assess if the incorporated cells were biologically responsive, Western blot analysis and quantitative polymerase chain reaction were used to assess the effects of interferon (IFN)-γ, and fluorescein isothiocyanate–dextran 4 kDa permeation was used to assess the effects of IFN-γ and tumor necrosis factor-α on barrier function. Results The optimal cell seeding density and flow rate were established. The continuous administration of flow resulted in the formation of polarized intestinal folds that contained Paneth cells, goblet cells, enterocytes, and enteroendocrine cells along with transit-amplifying and LGR5 + stem cells. Administration of IFN-γ for 1 hour resulted in the phosphorylation of STAT1, whereas exposure for 3 days resulted in a significant upregulation of IFN-γ related genes. Administration of IFN-γ and tumor necrosis factor-α for 3 days resulted in an increase in intestinal permeability. Conclusions We demonstrate that the Intestine-Chip is polarized, contains all the intestinal epithelial subtypes, and is biologically responsive to exogenous stimuli. This represents a more amenable platform to use organoid technology and will be highly applicable to personalized medicine and a wide range of gastrointestinal conditions.
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OoC devices have improved the characteristics of hPSC-derived pancreatic islets, intestinal, stomach, and liver organoids by supporting physiological flow rates.
“OoC devices have improved the characteristics of hPSC-derived pancreatic islets104, intestinal105, stomach106, and liver77 organoids by supporting physiological flow rates.”
From Organoids (2022) · cites this paper as [104]
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- Authors
- Workman, M. J., Gleeson, J. P., Troisi, E. J., Estrada, H. Q., Kerns, S. J., Hinojosa, C. D., Hamilton, G. A., Targan, S. R., Svendsen, C. N., & Barrett, R. J.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Emulate (United States) (US)
- Corresponding author
- Barrett, Robert J.
- ORCID
- Venue
- Cellular and Molecular Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2018
- Volume
- 5
- Issue
- 4
- Pages
- 669-677.e2
- ISSN
- 2352-345X (ISSN-L)
- PMC
- PMC6009013
- OpenAlex
- W2780753528
- Cited by
- 246
- References
- 28
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 31 · 2023: 26 · 2022: 23 · 2021: 38 · 2020: 45 · 2019: 32 · 2018: 13
- FWCI
- 11.08
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cellular and Molecular Gastroenterology and Hepatology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK106202-01)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- intestinal organoids, induced pluripotent stem cells, Paneth cells, goblet cells, enterocytes, enteroendocrine cells, Lgr5+ stem cells, interferon-gamma, TNF-α, STAT1 phosphorylation, intestinal permeability, barrier function
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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