Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research

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

Scientific Reports, 2024, 14, 10846

Number of Access:1,010（2026-04-06 22:40 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97220

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Title
Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research
Creator
CreatorName
Tong, Yanran
NRID
1000010904930 1000010904930
ORCID
0000-0002-3491-7955 0000-0002-3491-7955
researchmap permalink
toba-y toba-y
CreatorName
Ueyama Yukiko
researchmap permalink
ykt.jp ykt.jp
CreatorName
Yokota, Jumpei
CreatorName
Matsui, Hayato
CreatorName
Kanai, Masaki
NRID
1000050311387 1000050311387
researchmap permalink
read0165079 read0165079
Scopus Author ID
57195381326 57195381326
ORCID
0000-0003-0594-8178 0000-0003-0594-8178
CreatorName
Mizuguchi, Hiroyuki
Description
Tong Y., Ueyama-Toba Y., Yokota J., et al. Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research. Scientific Reports 14, 10846 (2024); https://doi.org/10.1038/s41598-024-61544-y.
Abstract
Human liver organoids are in vitro three dimensionally (3D) cultured cells that have a bipotent stem cell phenotype. Translational research of human liver organoids for drug discovery has been limited by the challenge of their low hepatic function compared to primary human hepatocytes (PHHs). Various attempts have been made to develop functional hepatocyte-like cells from human liver organoids. However, none have achieved the same level of hepatic functions as PHHs. We here attempted to culture human liver organoids established from cryopreserved PHHs (PHH-derived organoids), using HYDROX, a chemically defined 3D nanofiber. While the proliferative capacity of PHH-derived organoids was lost by HYDROX-culture, the gene expression levels of drug-metabolizing enzymes were significantly improved. Enzymatic activities of cytochrome P450 3A4 (CYP3A4), CYP2C19, and CYP1A2 in HYDROX-cultured PHH-derived organoids (Org-HYDROX) were comparable to those in PHHs. When treated with hepatotoxic drugs such as troglitazone, amiodarone and acetaminophen, Org-HYDROX showed similar cell viability to PHHs, suggesting that Org-HYDROX could be applied to drug-induced hepatotoxicity tests. Furthermore, Org-HYDROX maintained its functions for up to 35 days and could be applied to chronic drug-induced hepatotoxicity tests using fialuridine. Our findings demonstrated that HYDROX could possibly be a novel biomaterial for differentiating human liver organoids towards hepatocytes applicable to pharmaceutical research.
Publisher
Nature Research
Source Title
Scientific Reports
Volume (Issue)
14
Page
10846
Date of Issued
2024-05-13
Language
English
Handle URL
https://hdl.handle.net/11094/97220
eISSN
20452322
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1038/s41598-024-61544-y
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