Development and Characterization of a Human and Mouse Intestinal Epithelial Cell Monolayer Platform
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We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages. Ion transport phenotypes of monolayers from the proximal and distal colon and small intestine matched the known and unique physiology of these intestinal segments. The cultures secreted serotonin, GLP-1, and FGF19 and upregulated the epithelial sodium channel in response to known biologically active agents, suggesting intact secretory and absorptive functions. A screen of over 2,000 pharmacologically active compounds for inhibition of potassium ion transport in the mouse distal colon cultures led to the identification of a tool compound.
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Human intestinal organoid-derived monolayers have been successfully used to study host-pathogen interactions, epithelial barrier function, and various transport processes including secretion of hormones, growth factors, and ions, and absorption of glucose.
“Human intestinal organoid-derived monolayers have been successfully used to study host–pathogen interactions [10,11,12], epithelial barrier function [13], and various transport processes, including secretion of hormones, growth factors, and ions [14,15,16], and absorption of glucose [17].”
From Regulation of Enterocyte Brush Border Membrane Primary Na-Absorptive Transporters in Human Intestinal Organoid-Derived Monolayers (2024) · cites this paper as [14]
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References 31 · Cited by 179
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- Authors
- Kozuka, K., He, Y., Koo-McCoy, S., Kumaraswamy, P., Nie, B., Shaw, K., Chan, P., Leadbetter, M., He, L., Lewis, J. G., Zhong, Z., Charmot, D., Balaa, M., King, A. J., Caldwell, J. S., & Siegel, M.
- Affiliations
- Ardelyx (United States) (US)
- Silicon Valley University (US)
- Corresponding author
- Siegel, Matthew
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 9
- Issue
- 6
- Pages
- 1976-1990
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC5785676
- OpenAlex
- W2769549586
- Cited by
- 179
- References
- 31
- Citations by year
- 2026: 13 · 2025: 21 · 2024: 18 · 2023: 15 · 2022: 26 · 2021: 34 · 2020: 22 · 2019: 20 · 2018: 10
- FWCI
- 6.27
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (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, cc-by-sa)
- Funders
- Ardelyx
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Digestive system and related health
- Keywords
- human intestinal epithelium, small intestine, large intestine, colon, epithelial polarization, tight junctions, gene expression profiling, ion transport, epithelial sodium channel, serotonin release, glucagon-like peptide-1, FGF19, drug discovery
- MeSH terms
- Animals, Cell Differentiation, Fibroblast Growth Factors, Humans, Intestinal Mucosa, Intestine, Small, Serotonin, Gene Expression Regulation, Developmental, Cell Culture Techniques, Tight Junctions, Mice, Glucagon-Like Peptide 1
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