Development of a hepatic differentiation method in 2D culture from primary human hepatocyte-derived organoids for pharmaceutical research

Ueyama-Toba, Yukiko; Tong, Yanran; Yokota, Jumpei et al.

iScience, 2024, 27(9), 110778

Number of Access:1,345（2025-07-18 13:05 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98342

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Title
Development of a hepatic differentiation method in 2D culture from primary human hepatocyte-derived organoids for pharmaceutical research
Creator
NRID
1000010904930 1000010904930
ORCID
0000-0002-3491-7955 0000-0002-3491-7955
researchmap permalink
toba-y toba-y
CreatorName
Ueyama-Toba, Yukiko
CreatorName
Tong, Yanran
researchmap permalink
ykt.jp ykt.jp
CreatorName
Yokota, Jumpei
NRID
1000050867314 1000050867314
ORCID
0000-0001-8634-2922 0000-0001-8634-2922
researchmap permalink
murai_kazuhiro murai_kazuhiro
Scopus Author ID
57202460806 57202460806
CreatorName
Murai, Kazuhiro
NRID
1000020623044 1000020623044
researchmap permalink
hikitahayato hikitahayato
Scopus Author ID
23667454900 23667454900
CreatorName
Hikita, Hayato
NRID
1000090542118 1000090542118
researchmap permalink
abcdabcdabcd abcdabcdabcd
Scopus Author ID
7101627772 7101627772
CreatorName
Eguchi, Hidetoshi
NRID
1000070335355 1000070335355
researchmap permalink
takeharatetsuo takeharatetsuo
Scopus Author ID
7103332258 7103332258
CreatorName
Takehara, Tetsuo
NRID
1000050311387 1000050311387
researchmap permalink
read0165079 read0165079
Scopus Author ID
57195381326 57195381326
CreatorName
Mizuguchi, Hiroyuki
Description
Ueyama-Toba Yukiko, Tong Yanran, Yokota Jumpei, et al. Development of a hepatic differentiation method in 2D culture from primary human hepatocyte-derived organoids for pharmaceutical research. iScience 27, 110778 (2024); https://doi.org/10.1016/j.isci.2024.110778.
Abstract
Human liver organoids derived from primary human hepatocytes (PHHs) are expected to be a hepatocyte source for preclinical in vitro studies of drug metabolism and disposition. Because hepatic functions of these organoids remain low, it is necessary to enhance the hepatic functions. Here, we develop a novel method for two dimensional (2D)-cultured hepatic differentiation from PHH-derived organoids by screening several compounds, cytokines, and growth factors. Hepatic gene expressions in the hepatocyte-like cells differentiated from PHH-derived organoids (Org-HEPs) were greatly increased, compared to those in PHH-derived organoids. The metabolic activities of cytochrome P450 (CYP) 1A2, CYP2C8, CYP2C19, CYP2E1, and CYP3A4 were at levels comparable to those in PHHs. The cell viability of Org-HEPs treated with hepatotoxic drugs was almost the same as that of PHHs. Thus, PHH-derived organoids could be differentiated into highly functional hepatocytes in 2D culture. Thus, Org-HEPs will be useful for pharmaceutical research, including hepatotoxicity tests.
Publisher
Elsevier BV
Source Title
iScience
Volume (Issue)
27(9)
Page
110778
Date of Issued
2024-09-01
Language
English
Handle URL
https://hdl.handle.net/11094/98342
PISSN
25890042
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1016/j.isci.2024.110778
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Category
学術雑誌論文 Journal Article