ISSCR - Accelerating PSC-Derived Cell Therapies: Starting with the End in Mind

Induced pluripotent stem cell (iPSC)-derived brain models have become a fundamental tool for studying common neurological disorders, such as epilepsy, Alzheimer’s disease, and Parkinson’s disease. Being able to measure the electrical activity from these in vitro models in real time and label-free offers critical insights into the complexity of neuronal networks. Nowadays, the integration of single cell resolution with high-throughput physiological assays is especially valuable, as it can deepen our understanding of subtype-specific neuronal activity, yet it remains challenging to achieve.

In the present study, High-Density Microelectrode Array (HD-MEA) platforms (MaxWell Biosystems, Switzerland), were used to perform in vitro extracellular recordings of action potentials across entire neuronal networks, single neurons and even subcellular compartments. Additionally, we showed the advantages of having HD-MEA systems featuring 26,400 electrodes per well, since they play a crucial role in enhancing the statistical power gathered from iPSC-derived neurons over multiple days/weeks and in capturing even the smallest neuronal signals.

Finally, we present the Axon Tracking Assay, a tool for automated recording and analysis of individual axonal arbors of many neurons in parallel. The Axon Tracking Assay enabled the obtention of metrics such as potential conduction velocity, axonal length, and number of axonal branches. Therefore, with this unique method we characterized the function and axonal structure of different iPSC-derived neuronal cell lines.

Our HD-MEA platforms and the extracted metrics, such as firing rate, spike amplitude, and network burst profile among several others, provide an extremely powerful and user-friendly approach for in vitro drug screening and disease modelling.

‍