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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 &amp;gt; methylmercury chloride \u226b chlorpyrifos \u226b L-glutamate. Fifty nanomolar methylmercury chloride (MeHgCl) inhibited proliferation and induced apoptosis in early-stage cells. At the differentiated stage, 1 \u03bcM MeHgCl induced selective loss of S100\u03b2-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.<\/jats:p>","DOI":"10.1002\/stem.179","type":"journal-article","created":{"date-parts":[[2009,7,17]],"date-time":"2009-07-17T19:18:45Z","timestamp":1247858325000},"page":"2591-2601","source":"Crossref","is-referenced-by-count":105,"title":["A Human Stem Cell-Based Model for Identifying Adverse Effects of Organic and Inorganic Chemicals on the Developing Nervous System"],"prefix":"10.1093","volume":"27","author":[{"given":"Leonora","family":"Buzanska","sequence":"first","affiliation":[{"name":"NeuroRepair Department, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland"},{"name":"In-Vitro Methods Unit\/ECVAM, Institute for Health and Consumer Protection, European Commission, Joint Research Centre, Ispra, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Sypecka","sequence":"additional","affiliation":[{"name":"NeuroRepair Department, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Nerini-Molteni","sequence":"additional","affiliation":[{"name":"In-Vitro Methods Unit\/ECVAM, Institute for Health and Consumer Protection, European Commission, Joint Research Centre, Ispra, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Compagnoni","sequence":"additional","affiliation":[{"name":"In-Vitro Methods Unit\/ECVAM, Institute for Health and Consumer Protection, European Commission, Joint Research Centre, Ispra, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena T.","family":"Hogberg","sequence":"additional","affiliation":[{"name":"In-Vitro Methods Unit\/ECVAM, Institute for Health and Consumer 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