Long-term electrophysiological activity and pharmacological response of a human induced pluripotent stem cell-derived neuron and astrocyte co-culture

Biochem Biophys Res Commun. 2014 Jan 24;443(4):1176-81. doi: 10.1016/j.bbrc.2013.12.142. Epub 2014 Jan 7.

Abstract

Human induced pluripotent stem cell (hiPSC)-derived neurons may be effectively used for drug discovery and cell-based therapy. However, the immaturity of cultured human iPSC-derived neurons and the lack of established functional evaluation methods are problematic. We here used a multi-electrode array (MEA) system to investigate the effects of the co-culture of rat astrocytes with hiPSC-derived neurons on the long-term culture, spontaneous firing activity, and drug responsiveness effects. The co-culture facilitated the long-term culture of hiPSC-derived neurons for >3 months and long-term spontaneous firing activity was also observed. After >3 months of culture, we observed synchronous burst firing activity due to synapse transmission within neuronal networks. Compared with rat neurons, hiPSC-derived neurons required longer time to mature functionally. Furthermore, addition of the synapse antagonists bicuculline and 6-cyano-7-nitroquinoxaline-2,3-dione induced significant changes in the firing rate. In conclusion, we used a MEA system to demonstrate that the co-culture of hiPSC-derived neurons with rat astrocytes is an effective method for studying the function of human neuronal cells, which could be used for drug screening.

Keywords: Astrocyte co-culture; Human induced pluripotent stem cell-derived neurons; Long-term measurement; Multi-electrode array; Pharmacological effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Action Potentials / drug effects
  • Animals
  • Astrocytes / cytology
  • Astrocytes / drug effects*
  • Astrocytes / physiology*
  • Bicuculline / pharmacology
  • Cell Differentiation
  • Coculture Techniques
  • Drug Evaluation, Preclinical
  • Electrophysiological Phenomena
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / drug effects*
  • Induced Pluripotent Stem Cells / physiology*
  • Nerve Net / cytology
  • Nerve Net / drug effects
  • Nerve Net / physiology
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / physiology*
  • Neurotransmitter Agents / pharmacology
  • Rats
  • Synaptic Transmission

Substances

  • Neurotransmitter Agents
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Bicuculline