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ELECTROPHYSIOLOGICAL PHENOTYPE CHARACTERIZATION OF HUMAN IPSC-DERIVED DOPAMINERGIC NEURONAL LINES BY MEANS OF HIGH-RESOLUTION MICROELECTRODE ARRAYS

Michele Fiscella1, 2*, Noelle Leary1, Ebru Acun1, Silvia Ronchi1 and Andreas Hierlemann1
  • 1 ETH Zürich, Switzerland
  • 2 MaxWell Biosystems, Switzerland

High-resolution-microelectrode-array (MEA) technology enables to study neuronal dynamics at different scales, ranging from axonal physiology to network connectivity (Müller et. al, Lab on a Chip, 2015). We have used this MEA technology to characterize and compare the electrical phenotypes of commercially available human dopaminergic neurons (iCell DopaNeurons, MyCell DopaNeurons A53T α-synuclein, Cellular Dynamics International, Madison, WI, US). Furthermore, we have studied the effect of human astrocytes (iCell Astrocytes, Cellular Dynamics International, Madison, WI, US) on neural culture development. Astrocyte/neuron co-cultures showed higher signal amplitudes and higher firing rates than neural cultures without astrocytes. Adding astrocytes to neural cultures changed the whole culture morphology by promoting cell clustering. Interestingly, astrocyte/neuron co-cultures showed a lower sample-to-sample variability across multiple MEA recording sessions compared to neural cultures without astrocytes. We compared velocities of action potential propagation along axons between dopaminergic A53T α-synuclein neurons and the wild-type isogenic control cell line. We found that in both, wild-type and disease-model neurons, axonal action potential propagation velocities were lower than, for example, in rat primary cortical neurons (Bakkum et. al, Nature Communications, 2013). Furthermore, we found different axonal action-potential-velocity development profiles of A53T α-synuclein dopaminergic neurons and the wild-typecell line. Finally, we were able to precisely and reproducibly evoke action potentials in individual single human IPSC-derived neurons through subcellular-resolution electrical stimulation. High-resolution MEA systems enable to access novel electrophysiological parameters of iPSC-derived neurons, which can be potentially used as biomarkers for phenotype screening and drug testing.

Acknowledgements

EU, ERC Advanced Grant “neuroXscales” contract number 694829
EU, ERC-PoC “MwHresEP" contract number 755383
CH, Project CTI-No. 25933. 2 PFLS-LS “Multi-well electrophysiology platform for high-throughput cell-based assays”

References

J. Müller, M. Ballini, P. Livi, Y. Chen, M. Radivojevic, A. Shadmani, V. Viswam, I. L. Jones, M. Fiscella, R. Diggelmann, A. Stettler, U. Frey, D. J. Bakkum, A. Hierlemann, "High-resolution CMOS MEA platform to study neurons at subcellular, cellular, and network levels", Lab Chip, 2015, 15, pp. 2767-2780 (DOI: 10.1039/C5LC00133A)

Douglas J. Bakkum, Urs Frey, Milos Radivojevic, Thomas L. Russell, Jan Müller, Michele Fiscella, Hirokazu Takahashi, Andreas Hierlemann, "Tracking Axonal Action Potential Propagation on a High-density Microelectrode Array across Hundreds of Sites", Nature Communications, 2013, 4:2181 (DOI: 10.1038/ncomms3181).

Keywords: CMOS-MEAs, IPSC-derived neurons, Parkinson Disease, microelectrode arrays, phenotyping

Conference: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays, Reutlingen, Germany, 4 Jul - 6 Jul, 2018.

Presentation Type: Poster Presentation

Topic: Stem cell-derived applications

Citation: Fiscella M, Leary N, Acun E, Ronchi S and Hierlemann A (2019). ELECTROPHYSIOLOGICAL PHENOTYPE CHARACTERIZATION OF HUMAN IPSC-DERIVED DOPAMINERGIC NEURONAL LINES BY MEANS OF HIGH-RESOLUTION MICROELECTRODE ARRAYS. Conference Abstract: MEA Meeting 2018 | 11th International Meeting on Substrate Integrated Microelectrode Arrays. doi: 10.3389/conf.fncel.2018.38.00014

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Received: 05 Mar 2018; Published Online: 17 Jan 2019.

* Correspondence: Dr. Michele Fiscella, ETH Zürich, Zurich, Switzerland, michele.fiscella@mxwbio.com