A Human Stem Cell-Based Model for Identifying Adverse Effects of Organic and Inorganic Chemicals on the Developing Nervous System

Our aim was to investigate whether a human neural stem cell line, derived from umbilical cord blood (HUCB-NSC), can serve as a reliable test model for DNT. We assessed the sensitivity of HUCB-NSC at different developmental stages to a panel of neurotoxic (sodium tellurite, methylmercury chloride, cadmium chloride, chlorpyrifos and L-glutamate) and non-neurotoxic compounds (acetaminophen, theophylline and D-glutamate). In addition, we investigated the effect of some compounds on key neurodevelopmental processes like cell proliferation, apoptotic cell death and neuronal and glial differentiation. Less differentiated HUCB-NSCs were generally more sensitive to neurotoxicants with the notable exception of L-glutamate (L-Glu), which showed higher toxicity to later stages. The relative potency of the compounds was CdCl2>MeHgCl>>CPF>>L-Glu Fifty nanomolar methylmercury chloride (MeHgCl) inhibited proliferation and induced apoptosis in early stage cells. At the differentiated stage, 1 µM MeHgCl induced selective loss of S100ß expressing astrocytic cells. 1mM L-Glu did not influence early stages of HUCB-NSC development, but affected late stages of neuronal differentiation. A valuable system for in vitro DNT assessment should be able to discriminate between neurotoxic and non-neurotoxic compounds and show different susceptibility to chemicals according to developmental stage and cell lineage. Although not exhaustive, this work shows that the HUCB-NSC model fulfils these criteria and may serve as a human in vitro model for DNT priority setting.

LEONORA Buzanska;  SYPECKA Joanna;  NERINI MOLTENI Silvia;  COMPAGNONI Anna;  HÖGBERG Helena;  DEL TORCHIO Riccardo;  DOMANSKA-JANIK Krystyna;  ZIMMER Jens;  COECKE Sandra; 

2009-11-24

ALPHAMED PRESS

JRC52034

1066-5099,   

https://publications.jrc.ec.europa.eu/repository/handle/JRC52034,