Engineering circuits of human iPSC-derived neurons and rat primary glia

Frontiers in Neuroscience

Neuroscience

Isabelle Fruh¹  Matthias Müller¹  Tobias Ruff²  Leonardo Tognola²  János Vörös²  Sophie Girardin²  Arianna Menghini²  Stephan J. Ihle²  Magdalena Krubner²  Jens Duru² 

[1] Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Basel, Switzerland;Laboratory of Biosensors and Bioelectronics, Institute for Biomedical Engineering, Department of Electrical Engineering and Information Technology, University and ETH Zürich, Zürich, Switzerland;

关键词: bottom-up neuroscience;    iPSC-derived neurons;    glial cells;    in vitro;    microelectrode arrays;    magnesium;    drug testing;    spheroids;   

DOI  :  10.3389/fnins.2023.1103437

 received in 2022-11-20, accepted in 2023-04-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

Novel in vitro platforms based on human neurons are needed to improve early drug testing and address the stalling drug discovery in neurological disorders. Topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons have the potential to become such a testing system. In this work, we build in vitro co-cultured circuits of human iPSC-derived neurons and rat primary glial cells using microfabricated polydimethylsiloxane (PDMS) structures on microelectrode arrays (MEAs). Our PDMS microstructures are designed in the shape of a stomach, which guides axons in one direction and thereby facilitates the unidirectional flow of information. Such circuits are created by seeding either dissociated cells or pre-aggregated spheroids at different neuron-to-glia ratios. Furthermore, an antifouling coating is developed to prevent axonal overgrowth in undesired locations of the microstructure. We assess the electrophysiological properties of different types of circuits over more than 50 days, including their stimulation-induced neural activity. Finally, we demonstrate the inhibitory effect of magnesium chloride on the electrical activity of our iPSC circuits as a proof-of-concept for screening of neuroactive compounds.

【 授权许可】

Unknown   
Copyright © 2023 Girardin, Ihle, Menghini, Krubner, Tognola, Duru, Fruh, Müller, Ruff and Vörös.