A Scalable, Highly Reproducible Method for Creating 3-D Neural Constructs

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A Scalable, Highly Reproducible Method for Creating 3-D Neural Constructs

In a recent paper in PNAS, Michael P. Schwarz and co-authors describe a method for creating structurally complex, 3D neural constructs for neurotoxicity testing, by co-culturing human embryonic stem cell-derived neural progenitor cells, endothelial cells, mesenchymal cells, and microglia/macrophage precursors. The resulting neural constructs more closely replicate human brain tissue than monocultures or animal-derived cells, and include a variety of human neurological cell-types and connections that might be vulnerable to toxic exposures. The method also eliminates two significant problems associated with using primary human cells – limited availability and high variability between “batches.”

The authors used immunofluorescence imaging and gene expression data to verify cellular organization and functionality in the neural constructs. Next they exposed the constructs to 60 compounds including known toxic and nontoxic controls, collecting global gene expression data which they used to develop a toxin classification algorithm for a predictive computational model for neurotoxicity. (Some information about the model-building process and tissue-culturing methodology is provided in supplemental material to the article: http://www.pnas.org/content/suppl/2015/09/15/1516645112.DCSupplemental/pnas.1516645112.sapp.pdf) The computer model was then tested on a set of 10 blinded compounds (5 toxic, 5 control), and correctly classified 9 out of the 10. This result “compares favorably with the expected accuracy when using animal testing to predict human neurotoxicity.”

Citation: Schwartz, M.P., Hou, Z., Propson, N.E., et al. (2015). Human pluripotent stem cell-derived neural constructs for predicting neural toxicity. PNAS 112: 12516-12521, doi: 10.1073/pnas.1516645112

Posted: December 10, 2015

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