Re-aggregated brain cell culture as a sensitive in vitro model

Re-aggregated brain cell culture as a sensitive in vitro model to evaluate developmental/adult neurotoxicity: application for regulatory requirements

Speaker: Anna Price

Affiliation: In vitro Toxicology Unit,  European Centre for the Validation of Alternative Methods, 

Institute of Health and Consumer Protection, European Commission Joint Research Centre, Ispra (VA), Italy

Host: Paula Alves, Animal Cell Technology Unit
 

Abstract:

Chemicals present in the environment have a potential impact on neurodevelopment and children’s health. They may adversely affect the development of the nervous system in various ways perturbing commitment of neural stem cells, cell migration, synaptogenesis, cell death, formation of transmitters and receptors, trimming of connections, myelinisation and development of the blood-brain barrier. To address key biochemical and functional features of these processes appropriate cell culture techniques have been developed enabling application of in vitro approaches for DNT testing. Current OECD guidelines for the evaluation of neurotoxic effects of chemicals for hazard and risk assessment are based solely on in vivo studies evaluating mainly effects on neurobehaviour and neuropathology. Such approach is not suitable for testing a large number of chemicals (time-consuming, expensive and high number of animals is required). Implementation of in vitro tests to assess DNT effects of chemicals and pharmaceuticals where a battery of mechanistic assays is incorporated will be proposed.  Due to the complexity of the central nervous system the value of existing  in vitro models relevant for developmental neurotoxicity and toxicity of mature neurons (ranging from simple cell lines to complex brain reaggregates) will be discussed with a special emphasis on re-aggregated brain cell culture.  Additionally, sensitive and cell specific endpoints that are available to assess the impaired function of neurons or glial cells will be reviewed. Especially, the application of new emerging technologies such as measurements of electrical activity using multielectrode array (MEA) and metabolite profiling (metabolomics)  applied to re-aggregated brain cell culture will be evaluated.