[Strong demands for the new preclinical assessment system of the CNS adverse effects]

Nihon Yakurigaku Zasshi. 2020;155(5):295-298. doi: 10.1254/fpj.20029.
[Article in Japanese]

Abstract

Human induced pluripotent stem cell-derived neurons (hiPSC-neurons) have potentials to improve the predictability of the adverse effects (AEs) in the human central nervous system (CNS). We have succeeded in reproducing the human neural networks stably on dish. This is important because most of the CNS AEs were caused not by the neuronal death but by the abnormal neural network activities. Our group have been attempting to establish the in vitro assay system to detect abnormal neural network activities by microelectrode array system (MEA). Furthermore, the algorithm that can determine the synchronized burst firing (SBF) objectively was developed in the collaboration of our iPS Non-clinical Experiments for Nervous System (iNCENS) project and Consortium for Safety Assessment using Human iPS Cells (CSAHi). iNCENS and CSAHi are also involved in the international Life Sciences Institute (ILSI): Health and Environmental Sciences Institute (HESI) HESI NeuTox MEA sub team, and are participating in the pilot study using 12 compounds. In the big flow to develop physiological CNS safety assessment system, we have to show Japan initiative based on our innovative iPS technology we have developed so far.

MeSH terms

  • Action Potentials
  • Cells, Cultured
  • Humans
  • Induced Pluripotent Stem Cells*
  • Japan
  • Pilot Projects