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来自多能干细胞的多aminergic神经元用于研究发育神经毒性

Anna Kreutz^1,2, Guang Hu³, Erik Tokar⁴

¹Mechanistic Toxicology Branch, Division of Translational Toxicology, NIEHS, Research Triangle Park, Durham, NC, 27709, USA. anna.kreutz@nih.gov.

Stem cell reviews and reports

|June 5, 2023

概括

使用多能干细胞 (PSC) 的新体外方法可以选环境化学物质的发育神经毒性. 这种方法模拟了人类的神经发育,重点关注多巴胺基神经元发育,以填补数据缺口.

科学领域:

毒理学和发育生物学
在体外毒理学和干细胞研究.

背景情况:

传统的毒理学研究在评估众多商业化学品时面临着吞吐量限制.
由于数据稀缺和神经发育的复杂性,发育神经毒性 (DNT) 研究需要先进的方法.
目前用于DNT的体外试验方法缺乏模拟神经元亚型发展等关键过程的能力.

研究的目的:

审查现有的分化多能干细胞 (PSC) 到多巴胺基 (DA) 神经元的方法.
建议使用PSC衍生的DA神经元来选环境化学物质对神经发育的影响.
确定用于DNT风险评估的PSC应用中的相关技术和知识差距.

主要方法:

关于PSC分化协议进入DA神经元的科学文献的综述.
对DNT的当前体外新方法方法 (NAMs) 的分析.
建议将基于PSC的测定集成到DNT测试电池中.

主要成果:

已有几种已确定的协议存在,用于将PSC分化为DA神经元,回顾人类神经发育阶段.
公共服务中心提供了一个有希望的平台来建模特定的神经元亚型的发展,解决当前NAMs的局限性.
在DNT查中应用PSC可以提高风险评估策略的吞吐量和相关性.

结论:

多能干细胞非常适合在DNT评估中模拟人体体体内神经发育.
将PSC分化为多巴胺基神经元提供了一个有价值的模型,用于研究化学物质对特定神经通路的影响.
在DNT选电池中使用PSC代表了化学风险评估方法的重大进步.

关键词:

发育神经毒性发育神经毒性多巴氨基神经元是多巴氨基神经元.环境健康环境健康新方法方法论新方法方法论多能干细胞是多能干细胞.风险评估风险评估风险评估

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