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Neuron array advances toxicity testing
25 January 2010
Scientists in Germany have developed an alternative to animal testing for rapid screening and identification of chemicals that pose a health risk to the human nervous system.
Neurotoxicity laboratories worldwide face the daunting challenge of screening a growing catalogue of chemicals to identify those that could pose risk to human health, following the introduction of the EU's Reach legislation. Toxicity testing is traditionally done using animals but with spiraling costs in terms of cash and number of animals, reliable in vitro assays are needed. Lack of comparable read-outs between in vivo and in vitro systems can present problems, explains Jonathan West at the University of Dortmund, Germany, but West says he may have overcome this problem using a neural network.
Connections between the neurons are used to measure toxicity
Their new testing platform, called a network formation assay (NFA), monitors connections (or outgrowths) between specifically placed neurons and their neighbours. The formation of these connections is one of the basic principles of memory and learning, and its disturbance is frequently a clinical sign of neurotoxicity, says West. 'Because NFA examines neuron connections it represents an in vitro model that is comparable to the in vivo state', he adds.
West placed human neurons within a hexagonal array using cell patterning and could then easily monitor the formation of the network. Exposing the array to acrylamide, a neurotoxic reference compound inhibited network formation and distinguished between neurotoxic and cytotoxic effects. Without the need to locate the neurons or measure the lengths of the connections, means that a typical assay takes only three hours compared with up to 200 hours for manual testing.
'This simple and smart application of micro-engineered systems can significantly improve standard biological protocols', says Marco Cecchini, an expert in high-resolution patterning of biomaterials, at the National Enterprise for nanoScience and nanoTechnology, Pisa, Italy.
'NFA may also be applied within the context of reproductive toxicity testing, which is estimated to consume at least 60% of all animals required for Reach and is therefore the area in most need of novel in vitro assays ' adds Marcel Leist, University of Konstanz, Germany, who works on the project with West.
The team are currently working with teams around Europe to adapt NFA for use with neural stem cells but 'the real acid test will be whether or not NFA is adopted by neurotoxicology laboratories and accepted by regulatory authorities, ' says West.
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Link to journal article
The network formation assay: a spatially standardized neurite outgrowth analytical display for neurotoxicity screening
Jean-Philippe Frimat, Julia Sisnaiske, Subanatarajan Subbiah, Heike Menne, Patricio Godoy, Peter Lampen, Marcel Leist, Joachim Franzke, Jan G. Hengstler, Christoph van Thriel and Jonathan West, Lab Chip, 2010, 10, 701
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