Three-dimensional cell culture platform for high-throughput, high-content toxicity and differentiation screening of human neural progenitor cells

Nierode, Gregory James
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Dordick, Jonathan S.
Tessier, Peter M.
Karande, Pankaj
Gilbert, Ryan
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Chemical engineering
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This thesis is directed toward addressing both the poor understanding of how specific cell types respond to chemical exposure and the need to create new in vitro models that will be useful for predicting human toxicity. We hypothesize that undifferentiated human neural progenitor cells (hNPCs) and their differentiated neural progeny have different toxic sensitivities (i.e., different IC50 values) in response to chemical or drug exposure. To assess this, we have developed a microarray-based three-dimensional (3D) cell culture platform for high-throughput, high-content screening of toxicity and differentiation outcomes. Using the platform, we have grown and differentiated hNPCs in nanoscale 3D cultures and subsequently screened chemicals for cytotoxic effects. In doing so, we have begun to investigate how different types of human cells, such as neural progenitor cells and their differentiated progeny, respond differently to chemical stimuli. Furthermore, we have also used the platform to investigate the combinatorial effects of media additives on optimization of hNPC differentiation outcomes within 3D culture environments. Through these efforts, the impact of a 3D culture environment on stem/progenitor cell differentiation outcomes has begun to be evaluated, which will improve the future development of stem cell derived 3D culture models.
December 2017
School of Engineering
Dept. of Chemical and Biological Engineering
Rensselaer Polytechnic Institute, Troy, NY
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