Pelkonen Anssi, Mzezewa Ropafadzo, Sukki Lassi, Ryynänen Tomi, Kreutzer Joose, Hyvärinen Tanja, Vinogradov Andrey, Aarnos Laura, Lekkala Jukka, Kallio Pasi, Narkilahti Susanna
NeuroGroup, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Micro- and Nanosystems Research Group, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Biosens Bioelectron. 2020 Nov 15;168:112553. doi: 10.1016/j.bios.2020.112553. Epub 2020 Aug 26.
Epilepsies are a group of neurological disorders characterised by recurrent epileptic seizures. Seizures, defined as abnormal transient discharges of neuronal activity, can affect the entire brain circuitry or remain more focal in the specific brain regions and neuronal networks. Human pluripotent stem cell (hPSC)-derived neurons are a promising option for modelling epilepsies, but as such, they do not model groups of connected neuronal networks or focal seizures. Our solution is a Modular Platform for Epilepsy Modelling In Vitro (MEMO), a lab-on-chip device, in which three hPSC-derived networks are separated by a novel microfluidic cell culture device that allows controlled network-to-network axonal connections through microtunnels. In this study, we show that the neuronal networks formed a functional circuitry that was successfully cultured in MEMO for up to 98 days. The spontaneous neuronal network activities were monitored with an integrated custom-made microelectrode array (MEA). The networks developed spontaneous burst activity that was synchronous both within and between the axonally connected networks, i.e. mimicking both local and circuitry functionality of the brain. A convulsant, kainic acid, increased bursts only in the specifically treated networks. The activity reduction by an anticonvulsant, phenytoin, was also localised to treated networks. Therefore, modelling focal seizures in human neuronal networks is now possible with the developed chip.
癫痫是一组以反复癫痫发作为特征的神经系统疾病。发作被定义为神经元活动的异常短暂放电，可影响整个脑回路，或在特定脑区和神经元网络中更局限。人多能干细胞（hPSC）衍生的神经元是癫痫建模的一个有前景的选择，但就此而言，它们无法模拟相连的神经元网络群或局灶性发作。我们的解决方案是体外癫痫建模模块化平台（MEMO），一种芯片实验室设备，其中三个hPSC衍生的网络由一种新型微流控细胞培养设备隔开，该设备允许通过微隧道实现网络间可控的轴突连接。在本研究中，我们表明神经元网络形成了一个功能回路，该回路在MEMO中成功培养长达98天。使用集成的定制微电极阵列（MEA）监测自发的神经元网络活动。这些网络产生了自发的爆发活动，在轴突连接的网络内部和之间都是同步的，即模拟了大脑的局部和回路功能。惊厥剂 kainic 酸仅在经过特定处理的网络中增加爆发活动。抗惊厥药苯妥英钠导致的活动减少也局限于经过处理的网络。因此，利用开发的芯片现在可以在人类神经元网络中模拟局灶性发作。
