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Using Neural Progenitor Cells in High-Throughput Screens for Developmental Neurotoxicants: Triumphs and Tragedies
Citation:
SHAFER, TIM, M. Culbreth, J. M. Breier, AND W. R. MUNDY. Using Neural Progenitor Cells in High-Throughput Screens for Developmental Neurotoxicants: Triumphs and Tragedies. Presented at Society of Toxicology Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
Development of highthroughput screens (HTS) to detect and prioritize chemicals that may cause developmental neurotoxicity is needed to improve protection of public health.
Description:
Current protocols for developmental neurotoxicity testing are insufficient to test thousands of commercial chemicals. Thus, development of highthroughput screens (HTS) to detect and prioritize chemicals that may cause developmental neurotoxicity is needed to improve protection of public health. While a variety of cell culture models are amenable to this approach, neuroprogenitor (NP) cells, particularly those of human origin, may provide highly relevant models for developmental neurotoxicity testing. Over the past 5 years, we have examined the utility of different NP cell models for HTS assays of proliferation, apoptosls, viability and differentiation. Using ReNcell CX cells, a human cortical NP cell, we reliably measured changes in proliferation induced by known antiproliferative compounds as well as compounds known to cause developmental neurotoxicity. Furthermore, we have demonstrated that this approach is amenable to HTS by screening a set of 309 chemicals for effects on proliferation. More recently, we demonstrated that ReNcell CX cells are also useful for HTS assays for apoptosis. We have conducted more limited assessment of proliferation in other human neuroprogenitor cells models. Recently, we compared ReNcell CX cells to mouse cortical NP cells and demonstrated that both cell types are sensitive to compounds known to alter proliferation and/or apoptosis. Development of HTS assays for differentiation has been more challenging. NP cells tested to date have not differentiated rapidly, and it has been difficult to identify a cellular marker for committed neurons suitable for this endpoint. Our work demonstrates that NP cells can be utilized in HTS assays for the important neurodevelopmental endpoints of proliferation and apoptosls, but more development will be needed to use these cells in assays for neuroprogenitor differentiation. (This abstract does not reflect Agency Policy)