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

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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 μM MeHgCl induced selective loss of S100β-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 (US)
Pages (from-to)2591-2601
Number of pages11
JournalStem Cells
Volume27
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

Keywords

  • Developmental biology
  • Differentiation
  • Human cord blood
  • Neural stem cells
  • Proliferation
  • Toxicity

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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