Fungal brain infection modelled in a human- neurovascular-unit-on-a-chip with a functional blood?brain barrier

Title
Fungal brain infection modelled in a human- neurovascular-unit-on-a-chip with a functional blood?brain barrier
Authors
이수현최낙원김진이경태이종승신지수Baofang Cui양기석최이선이재현반용선조승우
Issue Date
2021-08
Publisher
Nature biomedical engineering
Citation
VOL 5-846
Abstract
The neurovascular unit, which consists of vascular cells surrounded by astrocytic end-feet and neurons, controls cerebral blood flow and the permeability of the blood?brain barrier (BBB) to maintain homeostasis in the neuronal milieu. Studying how some pathogens and drugs can penetrate the human BBB and disrupt neuronal homeostasis requires in vitro microphysiological models of the neurovascular unit. Here we show that the neurotropism of Cryptococcus neoformans―the most common pathogen causing fungal meningitis―and its ability to penetrate the BBB can be modelled by the co-culture of human neural stem cells, brain microvascular endothelial cells and brain vascular pericytes in a human-neurovascular-unit-on-a-chip maintained by a stepwise gravity-driven unidirectional flow and recapitulating the structural and functional features of the BBB. We found that the pathogen forms clusters of cells that penetrate the BBB without altering tight junctions, suggesting a transcytosis-mediated mechanism. The neurovascular-unit-on-a-chip may facilitate the study of the mechanisms of brain infection by pathogens, and the development of drugs for a range of brain diseases.
URI
http://pubs.kist.re.kr/handle/201004/73917
ISSN
2157-846X
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