Validating Well-Functioning Hepatic Organoids for Toxicity Evaluation
| Autor: | Seo Yoon Choi, Tae Hee Kim, Min Jeong Kim, Seon Ju Mun, Tae Sung Kim, Ki Kyung Jung, Il Ung Oh, Jae Ho Oh, Myung Jin Son, Jin Hee Lee |
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| Jazyk: | angličtina |
| Rok vydání: | 2024 |
| Předmět: | |
| Zdroj: | Toxics, Vol 12, Iss 5, p 371 (2024) |
| Druh dokumentu: | article |
| ISSN: | 2305-6304 47699299 |
| DOI: | 10.3390/toxics12050371 |
| Popis: | “Organoids”, three-dimensional self-organized organ-like miniature tissues, are proposed as intermediary models that bridge the gap between animal and human studies in drug development. Despite recent advancements in organoid model development, studies on toxicity using these models are limited. Therefore, in this study, we aimed to analyze the functionality and gene expression of pre- and post-differentiated human hepatic organoids derived from induced pluripotent stem cells and utilize them for toxicity assessment. First, we confirmed the functional similarity of this hepatic organoid model to the human liver through various functional assessments, such as glycogen storage, albumin and bile acid secretion, and cytochrome P450 (CYP) activity. Subsequently, utilizing these functionally validated hepatic organoids, we conducted toxicity evaluations with three hepatotoxic substances (ketoconazole, troglitazone, and tolcapone), which are well known for causing drug-induced liver injury, and three non-hepatotoxic substances (sucrose, ascorbic acid, and biotin). The organoids effectively distinguished between the toxicity levels of substances with and without hepatic toxicity. We demonstrated the potential of hepatic organoids with validated functionalities and genetic characteristics as promising models for toxicity evaluation by analyzing toxicological changes occurring in hepatoxic drug-treated organoids. |
| Databáze: | Directory of Open Access Journals |
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