Neural progenitor cells as models for high-throughput screens of developmental neurotoxicity: state of the science.
In vitro, high-throughput methods have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramifications for the accuracy, predictivity and sensitivity of the screening assays. In recent years neuroprogenitor cells from rodents and humans have become more widely available and may offer useful models having advantages over primary neuronal cultures and/or transformed cell lines. To date, these models have been utilized in only a limited number of toxicity studies. This review summarizes the state of the science regarding stem and neuroprogenitor models that could be used for screening assays, provides researchers in this field with examples of how these cells have been utilized to date, and discusses the advantages, limitations and knowledge gaps regarding these models. Data are available from both rodent and human stem and neuroprogenitor cell models that indicate that these models will be a valid and useful tool for developmental neurotoxicity testing. Full potential of these models will only be achieved following advances in neurobiology that elucidate differentiation pathways more clearly, and following further evaluation of larger sets of developmentally neurotoxic and non-toxic chemicals to define the sensitivity and predictivity of assays based on stem or progenitor cell models.
Breier
Joseph M
JM
The Curriculum in Toxicology, UNC School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gassmann
Kathrin
K
Kayser
Reinier
R
Stegeman
Hanneke
H
De Groot
Didima
D
Fritsche
Ellen
E
Shafer
Timothy J
TJ
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002490:Central Nervous System / Q000187:drug effects* / Q000254:growth & development; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000517:prevention & control; D013234:Stem Cells / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods*