Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research

Inui, Tatsuya; Uraya, Yusei; Yokota, Jumpei et al.

Stem Cell Research and Therapy, 2024, 15(1), 57

Number of Access:811（2025-08-16 14:04 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/95645

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Title
Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research
Creator
CreatorName
Inui, Tatsuya
CreatorName
Uraya, Yusei
CreatorName
Yokota, Jumpei
CreatorName
Yamashita, Tomoki
CreatorName
Kawai, Kanae
CreatorName
Okada, Kentaro
NRID
1000010904930 1000010904930
ORCID
0000-0002-3491-7955 0000-0002-3491-7955
researchmap permalink
toba-y toba-y
CreatorName
Ueyama-Toba, Yukiko
NRID
1000050311387 1000050311387
researchmap permalink
read0165079 read0165079
Scopus Author ID
57195381326 57195381326
CreatorName
Mizuguchi, Hiroyuki
Subject
Drug transporters
Drug-metabolizing enzymes
Intestinal organoids
iPS cell
Small intestine
Description
Inui T., Uraya Y., Yokota J., et al. Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research. Stem Cell Research and Therapy 15, 57 (2024); https://doi.org/10.1186/s13287-024-03685-5.
Abstract
Background: Human 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. Methods: To 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. Results: We 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. Conclusions: We have successfully improved the function and convenience of ELCs by utilizing organoid technology.
Publisher
BioMed Central Ltd
Source Title
Stem Cell Research and Therapy
Volume (Issue)
15(1)
Page
57
Date of Issued
2024-02-29
Language
English
Handle URL
https://hdl.handle.net/11094/95645
eISSN
17576512
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1186/s13287-024-03685-5
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article