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

Inui, Tatsuya; Uraya, Yusei; Yokota, Jumpei; Yamashita, Tomoki; Kawai, Kanae; Okada, Kentaro; Ueyama-Toba, Yukiko; Mizuguchi, Hiroyuki

doi:https://doi.org/10.1186/s13287-024-03685-5

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

アクセス数:764件（2025-07-18 13:59 集計）

固定URL: https://hdl.handle.net/11094/95645

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タイトル	Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research
著者	著者名 Inui, Tatsuya
	著者名 Uraya, Yusei
	著者名 Yokota, Jumpei
	著者名 Yamashita, Tomoki
	著者名 Kawai, Kanae
	著者名 Okada, Kentaro
	NRID 1000010904930 1000010904930 ORCID 0000-0002-3491-7955 0000-0002-3491-7955 researchmap permalink toba-y toba-y 著者名 Ueyama-Toba, Yukiko
	NRID 1000050311387 1000050311387 researchmap permalink read0165079 read0165079 Scopus Author ID 57195381326 57195381326 著者名 Mizuguchi, Hiroyuki
キーワード等	Drug transporters
	Drug-metabolizing enzymes
	Intestinal organoids
	iPS cell
	Small intestine
内容	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.
抄録	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.
出版者	BioMed Central Ltd
収録物名	Stem Cell Research and Therapy
巻(号)	15(1)
ページ	57
刊行年月	2024-02-29
言語	英語
ハンドルURL	https://hdl.handle.net/11094/95645
eISSN	17576512
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1186/s13287-024-03685-5
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCMI資源タイプ	text
DCTERMS.bibliographicCitation	Stem Cell Research and Therapy. 2024, 15(1), p. 57
DC.title	Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research
DC.creator	Inui, Tatsuya
	Uraya, Yusei
	Yokota, Jumpei
	Yamashita, Tomoki
	Kawai, Kanae
	Okada, Kentaro
	Ueyama-Toba, Yukiko
	Mizuguchi, Hiroyuki
DC.publisher	BioMed Central Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DC.type' scheme='DCTERMS.DCMIType	text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-02-29
DC.identifier	https://doi.org/10.1186/s13287-024-03685-5
DC.subject	Drug transporters
	Drug-metabolizing enzymes
	Intestinal organoids
	iPS cell
	Small intestine
DC.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.
DCTERMS.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.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	95645
citation_title	Functional intestinal monolayers from organoids derived from human iPS cells for drug discovery research
citation_author	Inui, Tatsuya
	Uraya, Yusei
	Yokota, Jumpei
	Yamashita, Tomoki
	Kawai, Kanae
	Okada, Kentaro
	Ueyama-Toba, Yukiko
	Mizuguchi, Hiroyuki
citation_publisher	BioMed Central Ltd
citation_language	英語
citation_date	2024-02-29
citation_journal_title	Stem Cell Research and Therapy
citation_volume	15
citation_issue	1
citation_firstpage	57
citation_doi	https://doi.org/10.1186/s13287-024-03685-5
citation_public_url	https://hdl.handle.net/11094/95645

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

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