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从形态和电生理学终点来评估药物的神经毒性,使用人类iPSC衍生的神经细胞模型

Zhe Qu¹, Shuangxing Li¹, Jingru Qiu¹

¹Key Laboratory of Quality Control and Non-clinical Research and Evaluation for Cellular and Gene Therapy Medicinal Products, Institute for Safety Evaluation, National Institutes for Food and Drug Control, Beijing, China.

Frontiers in cellular and infection microbiology

|February 27, 2026

概括

这项研究开发了一种人类诱导多能干细胞 (iPSC) 衍生的神经模型,用于评估药物神经毒性. 该模型有效评估神经元外生和神经网络功能,有助于更安全的药物开发.

科学领域:

干细胞生物学干细胞生物学
神经科学是一个神经科学.
毒理学毒理学毒理学

背景情况:

人类诱导的多能干细胞 (iPSCs) 对个性化医学和药物发现至关重要.
评估神经毒性对于药物开发至关重要,但传统方法不足.
标准化体外神经毒性测试缺乏监管指导.

研究的目的:

开发一种人类iPSC衍生的神经模型,用于评估神经毒性.
评估用于药物查的神经特异性形态学和电生理学终点.
为临床前安全性评估提供可靠的体外平台.

主要方法:

基因组编辑iPSCs的生成和分化为神经细胞.
使用iPSC衍生的神经模型进行神经细胞外生测试.
使用多电极阵列 (MEA) 记录来评估神经网络电生理学.

主要成果:

鉴定了各种化合物 (例如,酸,酸) 对神经元外生长的有毒作用.
观察到由化和阿曼塔丁对神经元激发的度依赖抑制.
演示了依赖于剂量和时间的乙胺醇和异化对神经活动的刺激/抑制作用.

结论:

开发的hiPSC衍生神经模型为神经毒性评估提供了高灵敏度和特定的终点.
这种模型有助于高通量药物查和神经治疗药物的安全风险评估.
该平台有望加强对具有潜在神经毒性药物的科学监督.

关键词:

电生理学活动电生理学活动.由hiPSC衍生的神经细胞.高分辨率成像技术的使用.微电极阵列检测检测微电极阵列检测神经细胞外生长的神经细胞外生长神经毒性的作用.

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