A Multi-Well Human iPSC Neuromuscular Disease Model on Elastomer Nanofibers

弹性体纳米纤维上的多孔人类 iPSC 神经肌肉疾病模型

• 批准号: 2723065
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2723065
• 关键词: Multi; Well; Human; iPSC; Neuromuscular

Motor neurons connect the CNS to muscle, yet the development and homeostasis ofthese synaptic connection is difficult to study in vitro, because contractile myofibersare unstable in standard culture systems. We propose to develop a human iPSCneuromuscularcircuit model, in which synthetic elastomer nanofibers support longtermstability, alignment and contraction of myofibers, innervated by motor neurons in96-well plates. Optogenetic stimulation of motor neurons will elicit myofibercontractions, providing a functional readout of neuromuscular transmission. Highcontentimaging is used to quantify axons, myofibers, and neuromuscular synapses.The model will be tested with circuits carrying mutations that affect nerve-muscleconnectivity.

运动神经元连接中枢神经系统和肌肉，然而这些突触连接的发育和稳态很难在体外研究，因为收缩性肌纤维在标准培养系统中是不稳定的。我们建议开发一个人类iPSC神经肌肉回路模型，其中合成弹性体纳米纤维支持96孔板中由运动神经元支配的肌纤维的长期稳定性、排列和收缩。运动神经元的光遗传刺激将引起肌纤维收缩，提供神经肌肉传递的功能读数。Highcontentimaging用于量化轴突、肌纤维和神经肌肉突触，该模型将用携带影响神经肌肉连接的突变的回路进行测试。