An important application for neural stem and progenitor cells is their use in neural toxicology assessments.
The motivation to develop alternative methods for assessing neurotoxicity has been facilitated by recent legislation in both Europe and the United States. This legislation has focused on controlling the risk of chemical effects on human health by prescribing the increased testing of chemicals and chemical products to predict their potential hazards, with emphasis on the use of emerging technologies and in vitro testing systems. This type of approach has been proposed by the National Research Council (NRC) Committee on Toxicity Testing and Assessment of Environmental Agents in the publication “Toxicity Testing in the Twenty-first Century: A Vision and a Strategy.”1
Additionally, and in response to a considerable rise in the incidence of neurodevelopmental disease in children and the large resource requirements of traditional methods, the push for new testing options for neurotoxicity has recently focused on developmental neurotoxicity testing (DNT). Workgroups in the United States and Europe have set forth proposals for the systematic evaluation of alternative methods for DNT, including the use of in vitro and non-mammalian test systems.2
For both adult and developmental neurotoxicity testing, the move away from whole-animal testing is dependent upon scientific advances in neurobiology that demonstrate the molecular and cellular basis of nervous system function. Then, increased emphasis needs to be placed on developing in vitro models based on human cell systems. While there are a number of human neuronal cell lines available, human neural stem cells show particular promise.3
Recently, neural stem cells of human origin have been immortalized to create clonal neural stem cell lines.4 Several human stem cell cultures that can be differentiated in mature cultures of neurons and glia are also commercially available. As assays for neurotoxicity using cells of human origin are compared with more widely used neural cell cultures of animal origin, it will become clear if there is a predictive improvement.
In the meantime, there will be market appetite for the development of standardized neurotoxicity assays using both human and animal neural stem cell lines.
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Footnotes:
1 National Research Council. “Toxicity testing in the twenty-first century: a vision and a strategy.” The National Academies Press. Available at: http://www8.nationalacademies.org/onpinews/newsitem.aspx?RecordID=11970. Accessed January 15, 2016.
2 Lein, P, Locke, P, Goldberg, A. “Meeting report: alternatives for developmental neurotoxicity testing. Enviro. Health Perspect 2007; 115, 764-768 2007.
3Mundy W. “Non-Animal Methods for Toxicity Testing. “Alternative Methods for Neurotoxicity”. U.S. Environmental Protection Agency, Neurotoxicology Division (B105-06). AltTox.org. Available at: http://www.alttox.org/ttrc/toxicity-tests/neurotoxicity/way-forward/. Accessed January 16, 2016.
4 De Filipis L, et al. “Immortalization of Human Neural Stem Cells with the c-Myc Mutant T58A.” Available at: http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0003310. Accessed January 16, 2016.