GSE171937
Human neurovascular unit chip with a functional blood-brain barrier models brain-infection mechanism of a fungal meningitis pathogen
Reconstitution of a neurovascular unit model with blood-brain barrier (BBB) function is of great importance for drug development targeting cerebral diseases and study of brain disease mechanisms. In this study, we describe a human neurovascular unit chip designed by reconstituting necessary cellular and extracellular components in microfluidic devices. Dynamic three-dimensional co-culture of human cells (neural stem cells, brain microvascular endothelial cells, and brain vascular pericytes) in microfluidics with a stepwise unidirectional flow successfully established the chip with BBB-mimetic structural and functional features to be an effective barrier for drugs and cytokines. Furthermore, we showed the utility of the chip by modeling the neurotropic behaviors and BBB penetration process of a global fungal meningitis pathogen, Cryptococcus neoformans. This chip is the first in vitro experimental model for monitoring neurotropism of C. neoformans and would contribute to the investigation of various cerebral disorders, including microbial infectious diseases and their corresponding drug development. Overall design: The NSCs in BHEM hydrogel on top of Transwell insert were co-cultured with ECs on the bottom of the Transwell.