| Autor: |
I. Pediaditakis, K. R. Kodella, D. V. Manatakis, C. Y. Le, S. Barthakur, A. Sorets, A. Gravanis, L. Ewart, L. L. Rubin, E. S. Manolakos, C. D. Hinojosa, K. Karalis |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.03.11.484005 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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