Abstract
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The access to human neurons from induced pluripotent stem cell (iPSC) technology has transformed the study of complex neurological diseases. FUJIFILM Cellular Dynamics, Inc. (FCDI) has recently developed iCell Induced Excitatory Neurons using transient overexpression of neurogenin 2 (NGN2) to produce a fully differentiated and highly pure population of human glutamatergic neurons. Furthermore, when co-cultured with iPSC-derived astrocytes (such as iCell Astrocytes 2.0), these neurons develop elaborate synaptic networks and exhibit synchronized activity that can be measured using High-Density Microelectrode Array (HD-MEA) technology.The promise of iPSC technology is the ability to create isogenic disease models and study them side-by-side in vitro. This application note incorporates iCell Induced Excitatory Neurons, which were differentiated from 1) an apparently healthy normal (AHN) iPSC line and 2) an engineered iPSC line featuring a heterozygous knockout mutation in the progranulin (GRN) gene. These cells were used to model the progressive neurodegenerative disorder frontotemporal dementia (FTD) and allowed for the in vitro investigation of cellular interactions and disease-specific phenotypes that may be difficult to replicate in animal models.MaxWell Biosystems’ HD-MEA technology offers a state-of-the-art platform for capturing the complexity of neuronal network development,[1] including both healthy and disease iPSC-derived models. The MaxTwo 24-Well Plate HD-MEA System, with 26,400 electrodes per well, enables simultaneous, non-invasive recordings of electrical activity with exceptional spatial resolution.This combination of high electrode density, small electrode size and excellent signal-to-noise ratio allows for high-sensitivity recordings from every active cell, ensuring the detection of even the most subtle phenotypes and generating robust data sets with high statistical power.By providing precise and direct access to neurons at the cellular level and their axons at the subcellular level, the MaxWell Biosystems’ advanced HD-MEA platform offers deeper insights into unique electrophysiological signatures and activity patterns associated with neurodegenerative and neurodevelopmental disorders. It allows for real-time capture of full network dynamics over extended culture periods, making it particularly useful for studying neurodegeneration or synaptic dysfunction, where network-level alterations may emerge gradually or occur as transient disease-related events. This application note demonstrates the capability of the MaxTwo 24-Well Plate in profiling network maturation in long-term co-cultures of iCell Induced Excitatory Neurons and iCell Astrocytes 2.0 – critical for disease modelling and drug discovery.