TY - JOUR
KW - Biomedical Engineering
KW - Cellular neuroscience
KW - Molecular neuroscience
AU - Iosif Pediaditakis
AU - Konstantia R. Kodella
AU - Dimitris V. Manatakis
AU - Christopher Y. Le
AU - Sonalee Barthakur
AU - Alexander Sorets
AU - Achille Gravanis
AU - Lorna Ewart
AU - Lee L. Rubin
AU - Elias S. Manolakos
AU - Christopher D. Hinojosa
AU - Katia Karalis
AB - Species differences in brain and blood-brain barrier (BBB) biology hamper the translation of findings from animal models to humans, impeding the development of therapeutics for brain diseases. Here, we present a human organotypic microphysiological system (MPS) that includes endothelial-like cells, pericytes, glia, and cortical neurons and maintains BBB permeability at in vivo 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.
BT - iScience
DA - 2022-08-19
DO - 10.1016/j.isci.2022.104813
IS - 8
LA - eng
N2 - Species differences in brain and blood-brain barrier (BBB) biology hamper the translation of findings from animal models to humans, impeding the development of therapeutics for brain diseases. Here, we present a human organotypic microphysiological system (MPS) that includes endothelial-like cells, pericytes, glia, and cortical neurons and maintains BBB permeability at in vivo 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.
PY - 2022
EP - 104813
T2 - iScience
TI - A microengineered Brain-Chip to model neuroinflammation in humans
VL - 25
SN - 2589-0042
ER -