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Neural Progenitor Cells as Models for High-Throughput Screens of Developmental Neurotoxicity: State of the Science
Citation:
BREIER, J. M., D. DE GROOT, E. FRITSCHE, K. GASSMANN, R. KAYSER, H. STEGEMAN, AND TIM J. SHAFER. Neural Progenitor Cells as Models for High-Throughput Screens of Developmental Neurotoxicity: State of the Science. NEUROTOXICOLOGY AND TERATOLOGY. Elsevier Science Ltd, New York, NY, 32(1):4-15, (2010).
Impact/Purpose:
In vitro models may be useful for the rapid toxicological screening of large numbers of chemicals for their potential to produce toxicity. Such screening could facilitate prioritization of resources needed for in vivo toxicity testing towards those chemicals most likely to result in adverse health effects. Cell cultures derived from nervous system tissue have proven to be powerful tools for elucidating cellular and molecular mechanisms of nervous system development and function, and have been used to understand the mechanism of action of neurotoxic chemicals. This review discusses the state of the science regarding the use of human and rodent stem and neuroprogenitor cells for toxicity testing purposes, with particular emphasis on developmental neurotoxicity. No such review is available at present, and thus this is timely and will serve as a resource for scientists as well as regulators who are generating or reviewing data generated with stem/neuroprogenitor cells, respectively.
Description:
In vitro, high-throughput approaches 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.
