Comparison of human biopsy-derived and human iPS cell-derived intestinal organoids established from a single individual

Rodent-derived intestinal tissues or human colon cancer-derived Caco-2 cells are widely used for in vitro pharmacokinetic tests. However, both entail problems such as species differences from humans and low expression levels of specific pharmacokinetic-related factors, respectively. To solve these p...

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Bibliographic Details
Published in:Drug metabolism and pharmacokinetics 2023-02, Vol.48, p.100482, Article 100482
Main Authors: Inui, Tatsuya, Yamashita, Tomoki, Tomita, Junya, Yokota, Jumpei, Kishimoto, Wataru, Nakase, Hiroshi, Mizuguchi, Hiroyuki
Format: Article
Language:English
Subjects:
Biopsy
Caco-2 Cells
Cell Differentiation
Endothelial Cells
Humans
Induced Pluripotent Stem Cells - metabolism
Intestinal first-pass effect
Intestinal Mucosa
Intestinal organoids
iPS cell
Monolayer culture
Organoids
Small intestine
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Summary:Rodent-derived intestinal tissues or human colon cancer-derived Caco-2 cells are widely used for in vitro pharmacokinetic tests. However, both entail problems such as species differences from humans and low expression levels of specific pharmacokinetic-related factors, respectively. To solve these problems, many groups, including ours, have been focusing on human biopsy-derived intestinal organoids (b-IOs) and human iPS cell-derived intestinal organoids (i-IOs). However, no reports directly compare the two. Therefore, we established both from a single individual and conducted a comparative study. b-IOs had a shorter doubling time than i-IOs: about 59 h vs 148 h. b-IOs also had higher gene expression levels of major drug transporters and drug-metabolizing enzymes than i-IOs. To evaluate their applicability to pharmacokinetics, both organoids were two-dimensionally cultured. Although the b-IO monolayer had a lower transepithelial electrical resistance than the i-IO monolayer, it had higher gene expression levels of many drug transporters and major drug-metabolizing enzymes than the i-IO monolayer. RNA-seq analysis showed that the i-IOs monolayer had a more complex structure than the b-IOs monolayer because the former contained neuronal and vascular endothelial cells. This study provides basic information for pharmacokinetic applications of human biopsy-derived and human iPS cell-derived intestinal organoids.
ISSN:1347-4367
1880-0920
DOI:10.1016/j.dmpk.2022.100482