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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Airman-on-a chip System Applied to Understanding Hyperoxic Oscillations

AFRL is using iPSC technology to develop personalized brain-on-a-chip microfluidic platforms harnessing cells from individual airmen. These platforms will provide insight into how an airman’s genetic background affects resiliency or susceptibility to operational conditions. The brain-on-a-chip platforms are comprised of iPSC-derived gluta- and gaba-minergic neurons, astrocytes, pericytes, and brain microvascular endothelial cells, and can allow investigations of complex blood-brain barrier neurovascular interactions. In current studies, the platforms are exposed to dynamic oxygen conditions simulating a fighter pilot’s oxygen exposure profiles, followed by comprehensive molecular analyses. In parallel, a matched human cohort is being evaluated in a hyperoxic chamber and physiologically and cognitively assessed. This study aligns in vitro work with in vivo human results to predict molecular outcomes and will provide a basis to predict an airman’s resiliency and target enhancement strategies for optimal performance.