验证功能良好的肝脏器官对毒性评估的验证
Seo Yoon Choi1, Tae Hee Kim1,2, Min Jeong Kim1
1Division of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Cheongju 28159, Republic of Korea.
Toxics
|May 24, 2024
概括
来自干细胞的人类肝脏器官在药物毒性测试中表现有前途. 这些经过验证的模型准确地区分了有毒和无毒物质,推动了药物开发安全性评估.
科学领域:
- 生物技术是生物技术.
- 药物开发 药物开发
- 毒理学 毒理学 毒理学
背景情况:
- 器官体是3D类似器官的组织,在药物开发中弥合了动物和人类的研究.
- 目前的有机体毒性研究是有限的,需要进一步的研究.
- 人类肝脏有机体为药物诱导的肝损伤评估提供了一个潜在的体外模型.
研究的目的:
- 分析由诱导多能干细胞衍生的人类肝脏器官的功能和基因表达.
- 使用这些有机物来评估已知的肝毒和非肝毒物质的毒性.
- 验证肝脏有机体作为药物毒性评估的可靠模型.
主要方法:
- 诱导的多能干细胞衍生肝脏器官被差异化和特征化.
- 功能性评估包括糖原储存,白蛋白/胆酸分泌和细胞染色体P450 (CYP) 活性.
- 毒性评估使用可纳,托格利塔,托尔卡 (肝毒性) 和糖,甲酸,生物素 (非肝毒性) 进行.
主要成果:
- 肝脏有机体表现出与人类肝脏的功能相似性.
- 器官模型成功地区分了肝毒性和非肝毒性物质.
- 分析了肝毒药物治疗器官的毒理变化,证实了模型的有效性.
结论:
- 功能验证的人类肝脏器官是药物毒性评估的有希望的模型.
- 这些有机体可以准确评估药物诱导的肝损伤.
- 肝脏有机体为推进临床前药物安全性测试提供了宝贵的工具.
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