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Cited by 82Pluripotent Stem Cells ResearchDrug Transport and Resistance MechanismsPharmacogenetics and Drug Metabolism

Generation of intestinal organoids derived from human pluripotent stem cells for drug testing

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Yoshida, Shinpei, Miwa, Hiroto, Kawachi, Tomoyuki, Kume, Shoen, Takahashi, Koji·2020·Scientific Reports
DOI 10.1038/s41598-020-63151-zPMC PMC7136241
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Abstract

Drug absorption via the intestinal tissue is modulated by membrane permeability and metabolism in intestinal epithelial cells (IECs). In drug discovery research, using human IECs to evaluate membrane permeability and metabolic stability can offer very useful information when exploring for drug candidate compounds that have good bioavailability and when trying to predict the fraction absorbed and intestinal availability in humans. Here, we evaluated the pharmacokinetic functions of human IECs differentiated from human induced pluripotent stem cells (hiPSCs) in 3D cultures. As human IECs differentiated in 3D cultures form intestinal organoids and spheroids (herein termed organoids), their morphology makes it difficult to evaluate their pharmacokinetic functions. Therefore, we dissociated intestinal organoids into single cells and attempted to purify human IECs. We found that hiPSC-derived IECs (hiPSC-IECs) expressed the epithelial cell adhesion molecule (EpCAM) and could be highly purified by sorting EpCAM+ cells. The hiPSC-IEC monolayer showed a high TEER value (approximately 350 Ω × cm 2). In addition, hiPSC-IECs oxidatively metabolized terfenadine (CYP3A and CYP2J2 substrate) and midazolam (CYP3A substrate). These results indicated that hiPSC-IECs form tight-junction and have cytochrome P450 enzymatic activities. In conclusion, we developed a novel application of hiPSC-derived intestinal organoids for drug testing.

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  • ALI culture has been widely employed for developing hiPSC-derived organoids such as cerebral organoids, kidney organoids, and intestinal organoids.

    “ALI culture has been widely employed for developing hiPSC-derived organoids, such as cerebral organoids, kidney organoids, and intestinal organoids [15, 26, 27].”

    From The empowering influence of air-liquid interface culture on skin organoid hair follicle development (2025) · cites this paper as [27]

    The Results section (no page number provided) confirms that the paper generated hiPSC-derived intestinal organoids. But the Methods describe embedding cells in Matrigel and overlaying them with culture medium; the paper does not identify this as air–liquid interface (ALI) culture or address cerebral and kidney organoids. It therefore supports the intestinal-organoid example, not the claimed use of ALI culture. (LLM, conf=0.85)

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References 32 · Cited by 82

Research works printed but not linked: 30

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Authors
Yoshida, S., Miwa, H., Kawachi, T., Kume, S., & Takahashi, K.
Affiliations
  • Tokyo Institute of Technology (JP)
  • Shionogi (Japan) (JP)
Corresponding author
Yoshida, Shinpei
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-04-06
Volume
10
Issue
1
Pages
5989-5989
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-63151-z
PMC
PMC7136241
OpenAlex
W3014228074
Cited by
82
References
32
Citations by year
2026: 8 · 2025: 6 · 2024: 16 · 2023: 11 · 2022: 17 · 2021: 19 · 2020: 5
FWCI
4.22
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Shionogi
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
intestinal organoids, human induced pluripotent stem cells, intestinal epithelial cells, drug absorption, membrane permeability, intestinal metabolism, EpCAM, cell sorting, tight junctions, CYP3A, CYP2J2, terfenadine, midazolam, 3D cell culture, drug testing
MeSH terms
Cell Line, Humans, Intestines, Midazolam, Organoids, Terfenadine, Induced Pluripotent Stem Cells

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