ArticleStem cell research & therapy2024
Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research.
Article in Stem cell research & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Nanofiber-Supported Decellularized Matrix Membrane Creates a Biomimetic Biochemical and Biophysical Niche for Intestinal Organoid Epithelium.Advanced healthcare materials · 2026Article
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Progress in human intestinal organoid research: applications to acute gastroenteritis viruses.Stem cell research & therapy · 2026Review
- Comparison of 2D, 3DBioengineering (Basel, Switzerland) · 2026Article
- Gut microbiota-M cell co-culture in inflammatory bowel disease and its therapeutic potential in organoid platforms.Frontiers in pharmacology · 2026Review
- Review
- Comparing the Altis RepliGut Organoid System to MDCK Monolayers in Predicting the Oral Absorption of Lenalidomide.Pharmaceutics · 2025Article
- Robust and reproducible human intestinal organoid-derived monolayer model for analyzing drug absorption.Scientific reports · 2025Article
- Advances and applications of gut organoids: modeling intestinal diseases and therapeutic development.Life medicine · 2025Review
- Organoids and tissue/organ chips.Stem cell research & therapy · 2024Article
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Authors and funding
8 authors.
Funding
Abstract
backgroundHuman induced pluripotent stem (iPS) cell-derived enterocyte-like cells (ELCs) are expected to be useful for evaluating the intestinal absorption and metabolism of orally administered drugs. However, it is difficult to generate large amounts of ELCs with high quality because they cannot proliferate and be passaged.
methodsTo solve the issue above, we have established intestinal organoids from ELCs generated using our protocol. Furthermore, monolayers were produced from the organoids. We evaluated the usefulness of the monolayers by comparing their functions with those of the original ELCs and the organoids.
resultsWe established organoids from ELCs (ELC-org) that could be passaged and maintained for more than a year. When ELC-org were dissociated into single cells and seeded on cell culture inserts (ELC-org-mono), they formed a tight monolayer in 3 days. Both ELC-org and ELC-org-mono were composed exclusively of epithelial cells. Gene expressions of many drug-metabolizing enzymes and drug transporters in ELC-org-mono were enhanced, as compared with those in ELC-org, to a level comparable to those in adult human small intestine. The CYP3A4 activity level in ELC-org-mono was comparable or higher than that in primary cryopreserved human small intestinal cells. ELC-org-mono had the efflux activities of P-gp and BCRP. Importantly, ELC-org-mono maintained high intestinal functions without any negative effects even after long-term culture (for more than a year) or cryopreservation. RNA-seq analysis showed that ELC-org-mono were more mature as intestinal epithelial cells than ELCs or ELC-org.
conclusionsWe have successfully improved the function and convenience of ELCs by utilizing organoid technology.
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