A Microengineered Brain-Chip to Model Neuroinflammation in Humans

Pediaditakis, I.; Kodella, K. R.; Manatakis, D. V.; Le, C. Y.; Barthakur, S.; Sorets, A.; Gravanis, A.; Ewart, L.; Rubin, L. L.; Manolakos, E. S.; Hinojosa, C. D.; Karalis, K.

doi:10.1101/2022.03.11.484005

bioRxiv · 10.1101/2022.03.11.484005

A Microengineered Brain-Chip to Model Neuroinflammation in Humans

Pediaditakis, I.·Kodella, K. R.·Manatakis, D. V.·Le, C. Y.·Barthakur, S.·Sorets, A.·Gravanis, A.·Ewart, L.·Rubin, L. L.·Manolakos, E. S.·Hinojosa, C. D.·Karalis, K.

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Abstract

Species 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-, 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.

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Pediaditakis, I., Kodella, K. R., Manatakis, D. V., Le, C. Y., Barthakur, S., Sorets, A., Gravanis, A., Ewart, L., Rubin, L. L., Manolakos, E. S., Hinojosa, C. D., Karalis, K.. 2022-03-14. A Microengineered Brain-Chip to Model Neuroinflammation in Humans. https://doi.org/10.1101/2022.03.11.484005

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