多能干细胞用于目标器官发育毒性测试的多能干细胞.
Xian Wu1,2, Yichang Chen1, Anna Kreutz1,3
1Mechanistic Toxicology Branch, Division of Translational Toxicology, NIEHS, Research Triangle Park, North Carolina 27709, USA.
概括
多能干细胞 (PSC) 为产前发育毒性测试提供了先进的模型. 包括有机体在内的2D和3DPSC模型的创新增强了与人类相关的评估,并减少了对动物试验的依赖.
科学领域:
- 发展性毒理学 发展性毒理学
- 干细胞生物学 干细胞生物学
- 替代测试方法 替代测试方法
背景情况:
- 产前发育毒性研究传统上依赖于动物试验,引发了伦理方面的担忧,并限制了人类的相关性.
- 多能干细胞 (PSC) 是开发与人类相关的体外模型的关键,用于研究胚胎和胎儿发育.
- 现有的2D PSC模型是可复制的,但缺乏体内复杂性,而有机体等3D模型提供更大的复杂性,但实施起来具有挑战性.
研究的目的:
- 审查最近使用人体PSC用于发育毒理学的进展.
- 探索新兴的工具和方法,以补充PSC模型来评估毒性.
- 突出这些创新如何支持更具预测性和监管认可的发育毒性评估.
主要方法:
- 使用人类多能干细胞 (PSCs) 分化成特定的血统 (例如大脑,心脏).
- 使用包括有机体在内的2D和3DPSC模型来模拟发育复杂性.
- 整合新的工具和技术与基于PSC的测试,以加强分析.
主要成果:
- 在应用PSC,特别是大脑和心脏器官的发展毒性研究方面取得了明显进展.
- 识别了将PSC模型与新方法方法 (NAM) 结合在一起的协同潜力.
- 展示了用于毒性查的更复杂和与人类相关的模型的开发.
结论:
- 人类PSC和像有机体这样的先进模型对于改善产前发育毒性评估至关重要.
- 创新技术与PSC模型的整合为更具预测性和道德健全的测试策略提供了途径.
- 这些进展支持监管决策,通过在开发过程中提供更相关,更可靠的化学和药物安全数据.
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