A microengineered Brain-Chip to model neuroinflammation in humans
Iosif Pediaditakis, Konstantia Kodella, Dimitris V. Manatakis, Christopher Y. Le, Sonalee Barthakur, Alexander G. Sorets, Achille Gravanis, Lorna Ewart, Lee L. Rubin, Ηλίας Σ. Μανωλάκος, Christopher D. Hinojosa, Katia Karalis
Abstract
relevant levels. This human Brain-Chip engineered to recapitulate critical aspects of the complex interactions that mediate neuroinflammation and demonstrates significant improvements in clinical mimicry compared to previously reported similar MPS. In comparison to Transwell culture, the transcriptomic profiling of the Brain-Chip displayed significantly advanced similarity to the human adult cortex and enrichment in key neurobiological pathways. Exposure to TNF-α recreated the anticipated inflammatory environment shown by glia activation, increased release of proinflammatory cytokines, and compromised barrier permeability. We report the development of a robust brain MPS for mechanistic understanding of cell-cell interactions and BBB function during neuroinflammation.