Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing
Interindividual differences in response to chemicals have been typically addressed through the use of a 10-fold default “uncertainty” factor. It was only recently that in vitro models emerged to quantitatively assess interindividual variability in the human population for specific chemicals. In the...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Current Research in Toxicology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666027X25000246 |
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| author | Xiugong Gao Rong Li Kayla Campasino Miranda R. Yourick Yang Zhao Robert L. Sprando Jeffrey J. Yourick |
| author_facet | Xiugong Gao Rong Li Kayla Campasino Miranda R. Yourick Yang Zhao Robert L. Sprando Jeffrey J. Yourick |
| author_sort | Xiugong Gao |
| collection | DOAJ |
| description | Interindividual differences in response to chemicals have been typically addressed through the use of a 10-fold default “uncertainty” factor. It was only recently that in vitro models emerged to quantitatively assess interindividual variability in the human population for specific chemicals. In the current study, we attempted to establish an in vitro model for assessing population variability in hepatotoxicity testing using a panel of hepatocytes derived from nine human induced pluripotent stem cell (iPSC) lines belonging to three different ethnic groups, Black or African American, Latino or Hispanic, and Non-Hispanic White. We demonstrated that the panel of iPSC-derived hepatocytes manifested diversity in hepatic function assays, in global and hepatic gene expressions, and in cytotoxic responses to four well know hepatotoxicants with distinct mechanisms of toxicity: acetaminophen, troglitazone, diglycolic acid, and usnic acid. However, due to the unavailability of model compounds with ethnicity specific toxicity as well as the small number of individuals in each ethnic group (n = 3), ethnic-specific effects were not observed using the model. |
| format | Article |
| id | doaj-art-ac05dcbe2de743cdb8269306ed2cd8f0 |
| institution | Kabale University |
| issn | 2666-027X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Toxicology |
| spelling | doaj-art-ac05dcbe2de743cdb8269306ed2cd8f02025-08-20T03:26:20ZengElsevierCurrent Research in Toxicology2666-027X2025-01-01810023810.1016/j.crtox.2025.100238Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testingXiugong Gao0Rong Li1Kayla Campasino2Miranda R. Yourick3Yang Zhao4Robert L. Sprando5Jeffrey J. Yourick6Corresponding author at: US FDA/HFP/OLOAS/OCT/DT, 8301 Muirkirk Rd, Laurel, MD 20708, United States.; Division of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United StatesDivision of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United StatesDivision of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United StatesDivision of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United StatesDivision of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United StatesDivision of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United StatesDivision of Toxicology, Office of Chemistry and Toxicology (OCT), Office of Laboratory Operations and Applied Science (OLOAS), Human Foods Program (HFP), U.S. Food and Drug Administration (FDA), Laurel, MD 20708, United StatesInterindividual differences in response to chemicals have been typically addressed through the use of a 10-fold default “uncertainty” factor. It was only recently that in vitro models emerged to quantitatively assess interindividual variability in the human population for specific chemicals. In the current study, we attempted to establish an in vitro model for assessing population variability in hepatotoxicity testing using a panel of hepatocytes derived from nine human induced pluripotent stem cell (iPSC) lines belonging to three different ethnic groups, Black or African American, Latino or Hispanic, and Non-Hispanic White. We demonstrated that the panel of iPSC-derived hepatocytes manifested diversity in hepatic function assays, in global and hepatic gene expressions, and in cytotoxic responses to four well know hepatotoxicants with distinct mechanisms of toxicity: acetaminophen, troglitazone, diglycolic acid, and usnic acid. However, due to the unavailability of model compounds with ethnicity specific toxicity as well as the small number of individuals in each ethnic group (n = 3), ethnic-specific effects were not observed using the model.http://www.sciencedirect.com/science/article/pii/S2666027X25000246In vitro modelPopulation variabilityEthnicityHepatotoxicityHepatocytesInduced pluripotent stem cell |
| spellingShingle | Xiugong Gao Rong Li Kayla Campasino Miranda R. Yourick Yang Zhao Robert L. Sprando Jeffrey J. Yourick Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing Current Research in Toxicology In vitro model Population variability Ethnicity Hepatotoxicity Hepatocytes Induced pluripotent stem cell |
| title | Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing |
| title_full | Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing |
| title_fullStr | Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing |
| title_full_unstemmed | Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing |
| title_short | Hepatocytes derived from human induced pluripotent stem cells: Towards establishing an in vitro model for assessing population variability in hepatotoxicity testing |
| title_sort | hepatocytes derived from human induced pluripotent stem cells towards establishing an in vitro model for assessing population variability in hepatotoxicity testing |
| topic | In vitro model Population variability Ethnicity Hepatotoxicity Hepatocytes Induced pluripotent stem cell |
| url | http://www.sciencedirect.com/science/article/pii/S2666027X25000246 |
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