Towards more physiological assays: iPSC-derived neurons tested on the 384 channel automated patch clamp platform Qube.
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Human-induced pluripotent stem cells (hiPSCs) can be differentiated into multiple cell types, including neurons and cardiomyocytes. This allows establishing novel, highly predictive human disease models in vitro. Ion channels represent a class of highly attractive therapeutic targets in the nervous and the cardiovascular system, rendering electrophysiological studies of hiPSCs important for their usage in drug discovery. However, such studies have traditionally been limited by the labor-intensive and low-throughput nature of the manual patch-clamp technique. In the present study, we used our automated, 384 channel patch clamp system Qube to develop robust assays for the study of hiPSC – derived neurons.
Three different hiPSC – based neuronal disease models were investigated. These hiPSC-derived neurons were generated from patients presenting either spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). In a first step, voltage – clamp was used to isolate and characterize individual endogenous currents and compare these to currents recorded from cells derived from healthy individuals. Both the SMA and ALS disease model exhibited elevated voltage-gated sodium channel (Nav) currents. We confirmed that the isogenic control cells of both models reverse the observed increase in Nav current. Finally, we tested a set of reference compounds, targeting various ion channels, on all three disease models and evaluated the assay with regard to stability and reproducibility.
Our recordings demonstrate the feasibility of assaying hiPSC-derived neurons on the APC platforms Qube. Altogether, these results can facilitate evaluating the use of hiPSC for early drug development and in extension personal medicine.