A microengineered Brain-Chip to model neuroinflammation in humans

• DOI: 10.1016/j.isci.2022.104813
• Publication Date: 2022-07-21T06:51:13Z
• Authors: Iosif Pediaditakis; Konstantia R. Kod...; Dimitris V. Manat...; Christopher Y. Le; Sonalee Barthakur; Alexander Sorets; Achille Gravanis; Lorna Ewart; Lee L. Rubin; Elias S. Manolakos; Christopher D. Hi...; Katia Karalis
• Keywords: 0301 basic medicine; 03 medical and health sciences; Science; Q; Molecular neuroscience; Biomedical engineering; Cellular neuroscience; Article

SUMMARYSpecies differences in the brain and the blood-brain barrier (BBB) biology hamper the translation from animal models to humans and impede the development of specific therapeutics for brain diseases. Here we present a human Brain-Chip engineered to recapitulate critical aspects of the complex brain cell-cell interactions that mediate neuroinflammation development. Our human organotypic microphysiological system (MPS) includes endothelial-like cells, pericytes, glia, and cortical neurons and maintains BBB permeability at in vivo relevant levels, providing a significant improvement in complexity and clinical mimicry compared to previous MPS models. This is the first report of a Brain-Chip with an RNA expression profile close to that of the adult human cortex and that demonstrates advantages over Transwell culture. Through perfusion of TNF-α, we recreated key inflammatory features, such as glia activation, the release of proinflammatory cytokines, and increased barrier permeability. Our model may provide a reliable tool for mechanistic studies in neuron-glial interactions and dysregulation of BBB function during neuroinflammation.