Electrical stimulation of stem cell-derived human neural networks for evaluating anti-seizure medications.

Journal: Epilepsia
Published Date: Jul 28, 2025

Abstract

OBJECTIVE: Current preclinical epilepsy drug screening relies on animal models that poorly reflect human neurophysiology, leading to high failure rates in clinical translation. We aimed to establish a human in vitro model using human-induced pluripotent stem cell (hiPSC)-derived cortical neurons cultured on multielectrode arrays (MEAs), capable of generating precisely controlled after-discharges (ADs) through electrical stimulation. We optimized stimulation parameters to evoke epileptiform-like hypersynchronous events and validated the model using six approved antiseizure medications (ASMs).

Authors

  • Joshua Nicholls
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Jinchao Gu
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Zhibin Chen
    Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Zikou Liu
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Ana Antonic-Baker
    Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
  • Muhammad Shahid Javaid
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Eliza Moore
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Hailin Zhu
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Afaf Altalhi
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • David K Wright
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.
  • Huseyin Sumer
    Department of Chemistry and Biotechnology, School of Science, Computing and Engineering Technologies, Swinburne University of Technology, Hawthorn, Victoria, Australia.
  • Terence J O'Brien
  • Patrick Kwan
  • Ben Rollo
    Department of Neuroscience, Faculty of Medicine, Nursing and Health Science, School of Translational Medicine, Monash University, Melbourne, Victoria, Australia.

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