Department of Biosystems Science and Engineering, ETH Zürich, Mattenstrasse 26, Basel, 4058, Switzerland.
MaxWell Biosystems AG, Albisriederstrasse 253, Zürich, 8047, Switzerland.
Adv Biol (Weinh). 2021 Mar;5(3):e2000223. doi: 10.1002/adbi.202000223. Epub 2021 Jan 14.
Recent advances in the field of cellular reprogramming have opened a route to studying the fundamental mechanisms underlying common neurological disorders. High-density microelectrode-arrays (HD-MEAs) provide unprecedented means to study neuronal physiology at different scales, ranging from network through single-neuron to subcellular features. In this work, HD-MEAs are used in vitro to characterize and compare human induced-pluripotent-stem-cell-derived dopaminergic and motor neurons, including isogenic neuronal lines modeling Parkinson's disease and amyotrophic lateral sclerosis. Reproducible electrophysiological network, single-cell and subcellular metrics are used for phenotype characterization and drug testing. Metrics, such as burst shape and axonal velocity, enable the distinction of healthy and diseased neurons. The HD-MEA metrics can also be used to detect the effects of dosing the drug retigabine to human motor neurons. Finally, it is shown that the ability to detect drug effects and the observed culture-to-culture variability critically depend on the number of available recording electrodes.
细胞重编程领域的最新进展为研究常见神经障碍的基本机制开辟了一条途径。高密度微电极阵列 (HD-MEAs) 提供了前所未有的手段来研究不同尺度的神经元生理学，从网络到单个神经元再到亚细胞特征。在这项工作中，HD-MEAs 在体外用于表征和比较人类诱导多能干细胞衍生的多巴胺能和运动神经元，包括模拟帕金森病和肌萎缩性侧索硬化症的同基因神经元系。可重复的电生理网络、单细胞和亚细胞指标用于表型特征描述和药物测试。burst shape 和轴突速度等指标可用于区分健康和患病神经元。HD-MEA 指标还可用于检测向人类运动神经元给药 retigabine 的效果。最后，结果表明，检测药物作用的能力和观察到的培养物间变异性严重依赖于可用记录电极的数量。
