A human stem cell-based model for identifying adverse effects of organic and inorganic chemicals on the developing nervous system

Leonora Buzanska, Joanna Sypecka, Silvia Nerini-Molteni, Anna Compagnoni, Helena T Hogberg, Riccardo del Torchio, Krystyna Domanska-Janik, Jens Zimmer, Sandra Coecke

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Abstract

The aim of our study 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 developmental neurotoxicity (DNT). We assessed the sensitivity of HUCB-NSCs at different developmental stages to a panel of neurotoxic (sodium tellurite, methylmercury chloride, cadmium chloride, chlorpyrifos, and L-glutamate) and non-neurotoxic (acetaminophen, theophylline, and D-glutamate) compounds. 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, which showed a higher toxicity to later stages. The relative potencies of the compounds were: cadmium chloride > methylmercury chloride >> chlorpyrifos >> L-glutamate. Fifty nanomolar methylmercury chloride (MeHgCl) inhibited proliferation and induced apoptosis in early-stage cells. At the differentiated stage, 1 muM MeHgCl induced selective loss of S100 beta-expressing astrocytic cells. One millimolar L-glutamate did not influence the early stages of HUCB-NSC development, but it 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 susceptibilities 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.
Original languageEnglish
JournalStem Cells
Volume27
Issue number10
Pages (from-to)2591-601
Number of pages10
ISSN1066-5099
DOIs
Publication statusPublished - 1. Oct 2009

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Buzanska, L., Sypecka, J., Nerini-Molteni, S., Compagnoni, A., Hogberg, H. T., del Torchio, R., Domanska-Janik, K., Zimmer, J., & Coecke, S. (2009). A human stem cell-based model for identifying adverse effects of organic and inorganic chemicals on the developing nervous system. Stem Cells, 27(10), 2591-601. https://doi.org/10.1002/stem.179