Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research

Inui, Jumpei; Ueyama-Toba, Yukiko; Imamura, Chiharu; Nagai, Wakana; Asano, Rei; Mizuguchi, Hiroyuki

doi:https://doi.org/10.1016/j.biomaterials.2025.123148

Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research

Inui, Jumpei; Ueyama-Toba, Yukiko; Imamura, Chiharu et al.

Biomaterials, 2025, 318, 123148

アクセス数:601件（2025-08-16 08:31 集計）

固定URL: https://hdl.handle.net/11094/100581

閲覧可能ファイル

ファイル	フォーマット	利用条件	サイズ	閲覧回数	利用開始日	説明	information
Biomaterials_318_123148	pdf	なし	9.09 MB	52	2025.03.14

Creative Commons : 表示 - 非営利 - 改変禁止

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

タイトル	Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research
著者	著者名 Inui, Jumpei
	NRID 1000010904930 1000010904930 ORCID 0000-0002-3491-7955 0000-0002-3491-7955 researchmap permalink toba-y toba-y 著者名 Ueyama-Toba, Yukiko
	著者名 Imamura, Chiharu
	著者名 Nagai, Wakana
	著者名 Asano, Rei
	NRID 1000050311387 1000050311387 researchmap permalink read0165079 read0165079 Scopus Author ID 57195381326 57195381326 著者名 Mizuguchi, Hiroyuki
キーワード等	Drug metabolism
	Drug-induced hepatotoxicity
	Hepatic organoids
	Human induced pluripotent stem cells
内容	Inui J., Ueyama-Toba Y., Imamura C., et al. Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research. Biomaterials 318, 123148 (2025); https://doi.org/10.1016/j.biomaterials.2025.123148.
抄録	Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (HLCs) are expected to replace primary human hepatocytes (PHHs) as a new stable source of hepatocytes for pharmaceutical research. However, HLCs have lower hepatic functions than PHHs, require a long time for differentiation and cannot be prepared in large quantities because they do not proliferate after their terminal differentiation. To overcome these problems, we here established hepatic organoids (iHOs) from HLCs. We then showed that the iHOs could proliferate approximately 105-fold by more than 3 passages and expressed most hepatic genes more highly than HLCs. In addition, to enable their widespread use for in vitro drug discovery research, we developed a two-dimensional culture protocol for iHOs. Two-dimensionally cultured iHOs (iHO-Heps) expressed most of the major hepatocyte marker genes at much higher levels than HLCs, iHOs, and even PHHs. The iHO-Heps exhibited glycogen storage capacity, the capacity to uptake and release indocyanine green (ICG), albumin and urea secretion, and the capacity for bile canaliculi formation. Importantly, the iHO-Heps had the activity of major drug-metabolizing enzymes and responded to hepatotoxic drugs, much like PHHs. Thus, iHO-Heps overcome the limitations of the current models and promise to provide robust and reproducible pharmaceutical assays.
出版者	Elsevier Ltd
収録物名	Biomaterials
巻(号)	318
ページ	123148
刊行年月	2025-07-01
言語	英語
ハンドルURL	https://hdl.handle.net/11094/100581
PISSN	01429612
eISSN	18785905
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1016/j.biomaterials.2025.123148
アクセス権	open access
権利情報	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 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
DCTERMS.bibliographicCitation	Biomaterials. 2025, 318, p. 123148
DC.title	Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research
DC.creator	Inui, Jumpei
	Ueyama-Toba, Yukiko
	Imamura, Chiharu
	Nagai, Wakana
	Asano, Rei
	Mizuguchi, Hiroyuki
DC.publisher	Elsevier Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2025-07-01
DC.identifier	https://doi.org/10.1016/j.biomaterials.2025.123148
DC.subject	Drug metabolism
	Drug-induced hepatotoxicity
	Hepatic organoids
	Human induced pluripotent stem cells
DC.description	Inui J., Ueyama-Toba Y., Imamura C., et al. Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research. Biomaterials 318, 123148 (2025); https://doi.org/10.1016/j.biomaterials.2025.123148.
DCTERMS.abstract	Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (HLCs) are expected to replace primary human hepatocytes (PHHs) as a new stable source of hepatocytes for pharmaceutical research. However, HLCs have lower hepatic functions than PHHs, require a long time for differentiation and cannot be prepared in large quantities because they do not proliferate after their terminal differentiation. To overcome these problems, we here established hepatic organoids (iHOs) from HLCs. We then showed that the iHOs could proliferate approximately 105-fold by more than 3 passages and expressed most hepatic genes more highly than HLCs. In addition, to enable their widespread use for in vitro drug discovery research, we developed a two-dimensional culture protocol for iHOs. Two-dimensionally cultured iHOs (iHO-Heps) expressed most of the major hepatocyte marker genes at much higher levels than HLCs, iHOs, and even PHHs. The iHO-Heps exhibited glycogen storage capacity, the capacity to uptake and release indocyanine green (ICG), albumin and urea secretion, and the capacity for bile canaliculi formation. Importantly, the iHO-Heps had the activity of major drug-metabolizing enzymes and responded to hepatotoxic drugs, much like PHHs. Thus, iHO-Heps overcome the limitations of the current models and promise to provide robust and reproducible pharmaceutical assays.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	100581
citation_title	Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research
citation_author	Inui, Jumpei
	Ueyama-Toba, Yukiko
	Imamura, Chiharu
	Nagai, Wakana
	Asano, Rei
	Mizuguchi, Hiroyuki
citation_publisher	Elsevier Ltd
citation_language	英語
citation_date	2025-07-01
citation_journal_title	Biomaterials
citation_volume	318
citation_firstpage	123148
citation_doi	https://doi.org/10.1016/j.biomaterials.2025.123148
citation_public_url	https://hdl.handle.net/11094/100581

Two-dimensionally cultured functional hepatocytes generated from human induced pluripotent stem cell-derived hepatic organoids for pharmaceutical research

閲覧可能ファイル

論文情報

論文詳細を表示