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生成功能性大脑区域特定的神经球体,用于高通量查

Jiajing Zhang¹, Angelica Medina¹, Marc Ferrer²

¹Division of Preclinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Rockville, MD, USA.

Methods in molecular biology (Clifton, N.J.)

|February 18, 2025

概括

开发先进的神经球体为研究神经退行性疾病提供了可扩展的解决方案. 这些3D大脑模型通过模拟大脑区域的复杂性和监测神经活动,使得强大的药物发现和毒性测试成为可能.

科学领域:

神经科学是一个神经科学.
干细胞生物学干细胞生物学
药物发现药物发现药物发现

背景情况:

神经退行性疾病研究需要相关的,可扩展的细胞模型来开发药物.
现有的模型往往缺乏有效性和毒性测试所需的复杂性和预测能力.
神经球体提供了一个功能,多功能和可扩展的3D大脑模型解决方案.

研究的目的:

介绍一个详细的方法来产生功能性的,脑区域特定的神经球体.
为监测神经网络活动建立与高通量选 (HTS) 兼容的试验.
为了证明这些球体对于疾病建模和化合物查的实用性.

主要方法:

人类诱导的多能干细胞 (hiPSC) 衍生的神经元和星体在特定比例的聚合.
形成无支架的3D大脑区域特定球形 (例如PFC,VTA).
开发一种与HTS兼容的测定方法,测量振荡,以监测神经网络活动.

主要成果:

成功生成功能性,特定于大脑区域的神经球体.
对神经网络活动进行HTS兼容的振荡监测的演示.
验证球形多功能性用于模拟神经异质性.

结论:

神经球体为神经退行性疾病研究提供了一个强大而可扩展的平台.
这种方法可以对神经网络进行功能评估,并支持用于药物发现的HTS.
该平台的多功能性允许通过结合多种细胞类型来建模各种神经疾病.

关键词:

像大脑区域一样的大脑区域.的振荡的振荡.疾病建模疾病建模药物发现药物发现功能读取功能读取结果高通量选的高通量选人类诱导的多能干细胞分化脑细胞.神经球体是神经球体.三维文化的三维文化

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