A human stem cell‑derived test system for agents modifying neuronal N‑methyl‑d‑aspartate‑type glutamate receptor Ca2+‑signalling

Klima S, Brüll M, Spreng A-S, Suciu I, Falt T, Schwamborn JC, Waldmann T, Karreman C, Leist M.

Archives of Toxicology, 2021


In order to assess neuronal functional receptors in vitro the authors developed a pluripotent stem cell (PSC)-based neural culture capable of forming a functional neural network.  The mixed cortical culture could be generated in 24 days from NESC (neuroepithelial stem cell) population.  Characterization including functional tests on Axion's multiwell multielectrode array system were performed.  The results showed various functional neurotransmitter receptors, including NMDA-R.   

The NMDA receptor plays a critical role in synaptic plasticity in the hippocampus and disturbance of the receptor is linked to neurological diseases such as Alzheimer's Disease.   Therefore several modulators of NMDA-R have been developed as drug candidates. Additionally, NMDA-R's are involved in toxicological AOPs.

This receptor is not found on conventional neural cell lines nor most stem cell-derived neurons therefore they focused on characterizing the Ca2+ signaling.  This MCC population developed in this publication may provide part of a test system able to characterize the effects of chemicals on neurotransmitters.