BioCentury
ARTICLE | Distillery Techniques

Techniques: Neuronal cell culture-based model of the human cortex for screening neuroprotective therapies and disease modeling

April 14, 2016 7:00 AM UTC

A neuronal cell culture-based model of the human cortex could be useful for screening neuroprotective compounds and generating models of specific neurological diseases. The model involved generating rosette-type neural stem cells (NSCs) from human embryonic stem cells (ESCs) or banked induced pluripotent stem (iPS) cells, isolating forkhead box G1 (FOXG1)-expressing neural precursor cell clusters from the NSCs, and treating the FOXG1-expressing precursor cells with retinoic acid to induce differentiation into multiple excitatory and inhibitory neuronal subtypes that formed networks representative of all six layers of the human cortex. In the cortical culture model subjected to NMDA receptor- or oxygen/glucose deprivation-mediated excitotoxicity, the poly ADP-ribose polymerase (PARP) inhibitors Lynparza olaparib, rucaparib, veliparib, or talazoparib decreased cell death compared with vehicle. Next steps could include using the cortical model to generate cell-based, disease-specific models of schizophrenia, autism or Alzheimer's disease (AD).

AstraZeneca plc markets Lynparza to treat ovarian cancer and has the compound in Phase I to Phase III testing to treat other solid tumor types...