验证用于毒性评估的功能良好的肝脏器官模型

Toxics Pub Date : 2024-05-17 DOI:10.3390/toxics12050371
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
{"title":"验证用于毒性评估的功能良好的肝脏器官模型","authors":"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","doi":"10.3390/toxics12050371","DOIUrl":null,"url":null,"abstract":"“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.","PeriodicalId":508978,"journal":{"name":"Toxics","volume":"73 6","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Validating Well-Functioning Hepatic Organoids for Toxicity Evaluation\",\"authors\":\"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\",\"doi\":\"10.3390/toxics12050371\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"“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.\",\"PeriodicalId\":508978,\"journal\":{\"name\":\"Toxics\",\"volume\":\"73 6\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-05-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxics\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/toxics12050371\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/toxics12050371","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

"类器官 "是一种三维自组织器官样微型组织,被认为是药物开发过程中弥合动物研究与人体研究之间差距的中间模型。尽管近年来类器官模型的开发取得了进展,但利用这些模型进行的毒性研究还很有限。因此,在本研究中,我们旨在分析诱导多能干细胞分化前和分化后人肝脏器官组织的功能和基因表达,并将其用于毒性评估。首先,我们通过各种功能评估,如糖原储存、白蛋白和胆汁酸分泌以及细胞色素P450(CYP)活性,证实了这种肝脏类器官模型与人类肝脏在功能上的相似性。随后,我们利用这些经过功能验证的肝脏类器官组织,对三种已知会导致药物性肝损伤的肝毒性物质(酮康唑、曲格列酮和托卡朋)和三种非肝毒性物质(蔗糖、抗坏血酸和生物素)进行了毒性评估。有机体能有效区分有肝毒性和无肝毒性物质的毒性水平。我们通过分析肝毒性药物处理过的器官组织中发生的毒性变化,证明了具有有效功能和遗传特征的肝脏器官组织作为毒性评估模型的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Validating Well-Functioning Hepatic Organoids for Toxicity Evaluation
“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.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信