Multicellular, organotypic engineered cell cultures have the potential to bridge the multi-scale knowledge gaps between molecular pathways of action and tissue-level physiological responses; however, interpretation of these data requires a rigorous mathematical framework to define and describe complex interactions among cells. We have developed a novel and scalable cell culture system incorporating astrocytes and microglia into a three-dimensional matrix to study the potential neuroinflammatory responses of glia to chemical exposures. The system is amenable to biochemical and imaging-based assays, and it was exposed to environmental toxicants with neurological effects. Data obtained from this construct are used to generate and test mathematical cell–cell interaction models, representing the nature and magnitude of heterotypic cell–cell interactions in the brain's inflammatory responses to environmental toxicants.
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