Author:
Date:
2021-03-05
[Abstract] The high attrition rate in drug development processes calls for additional human-based model systems. However, in the context of brain disorders, sampling live neuronal cells for compound testing is not applicable. The use of human induced pluripotent stem cells (iPSCs) has revolutionized the field of neuronal disease modeling and drug discovery. Thanks to the development of iPSC-based neuronal differentiation protocols, including tridimensional cerebral organoids, it is now possible to molecularly dissect human neuronal development and human brain disease pathogenesis in a dish. These approaches may allow dissecting patient-specific treatment efficacy in a disease-relevant cellular context. For drug discovery approaches, however, a highly reproducible and cost-effective cell model is ...
[摘要] [摘要]药物开发过程中的高流失率要求使用其他基于人的模型系统。但是,在脑部疾病的情况下,不适合对活的神经元细胞进行采样以进行化合物测试。人类诱导的多能干细胞(iPSC )的使用彻底改变了神经元疾病建模和药物发现领域。由于基于iPSC的神经元分化方案(包括三维脑类器官)的发展,现在可以在一个碟子中分子解剖人神经元发育和人脑疾病的发病机理。这些方法可以允许在与疾病相关的细胞环境中解剖患者特异性的治疗功效。但是,对于药物发现方法,需要高度可复制且具有成本效益的细胞模型。在这里,我们描述了一种一步-步骤,用于从人产生健壮和可膨胀的神经祖细胞(NPC)工艺的iPSC 。用此协议生成的NPC是同质的且高度增殖。这些功能使NPC适合开发用于药物发现的高通量化合物筛选。人iPSC衍生的NPC示出了代谢依赖于线粒体活性,因此可也用于研究神经病症,其中线粒体功能受到影响。该协议涵盖了制备,培养和表征人iPSC来源的NPC所需的所有步骤。
图形摘要:
示意性的协议的所述发电机密封的离子人类源自iPSC的的NPC
[背景技术]近年来,目标为中心的药物发现的缺点已经用于寻址的神经系统疾病的方案变得明显,特别是(保罗等人,2010) ...
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