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Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity
Citation:
Druwe, I., Tim Shafer, K. Wallace, P. Valdivia, AND W. Mundy. Induced pluripotent stem cell-derived neuron as a human model for testing environmentally induced developmental neurotoxicity. Presented at Society of Toxicology Meeting, Phoenix, AZ, March 23 - 27, 2014.
Impact/Purpose:
Abstract will be presented at Society of Toxicology Meeting, March 23-27, 2014, Phoenix, AZ
Description:
Induced pluripotent stem cell-derived neurons as a human model for testing environmentally induced developmental neurotoxicity Ingrid L. Druwe1, Timothy J. Shafer2, Kathleen Wallace2, Pablo Valdivia3 ,and William R. Mundy2. 1University of North Carolina, Curriculum in Toxicology, Chapel Hill, NC. 2Integrated Systems Toxicology Division, NHEERL, USEPA, RTP, NC, 3Axion Biosystems, Atlanta GA, USA. Exposure to environmental toxicants during development and early childhood can result in adverse effects in the developing nervous system. Because of the cost and time required, most chemicals currently in commerce have not been evaluated for developmental neurotoxicity (DNT). To date, methods to screen for chemical effects on the critical events of DNT (e.g. proliferation, migration, neurite outgrowth, synaptogenesis) have utilized both human and rodent cell lines or primary rodent neural cultures. Unfortunately, chemical effects in rodent models do not always extrapolate to humans due to species-specific mechanisms and pathways. This talk will center around two cell-based assays that utilize human induced pluripotent stem cell (iPSC)-derived neurons to assess the impact of environmental chemicals on DNT. High content analysis of neurite outgrowth and synaptogenesis were examined in both rodent neurons and human iPSC using a “training set” of chemicals with known effects in vitro. Multi-electrode array technology monitors the functional development of neuronal electrical and network activity. Together these techniques and technologies offer a viable high throughput screening option for testing both existing and newly created environmental chemicals. This abstract does not necessarily reflect USEPA policy.