学術雑誌論文

学術雑誌論文

iScience. 2024, 27(9), p. 110778

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

Elsevier BV

英語

2024-09-01

https://doi.org/10.1016/j.isci.2024.110778

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.

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.

This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

98342

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

Elsevier BV

英語

2024-09-01

iScience

27

9

110778

https://doi.org/10.1016/j.isci.2024.110778

https://hdl.handle.net/11094/98342