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

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Title
Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood–brain barrier
Author(s)
Jin Kim; Kyung-Tae Lee; Jong Seung Lee; Jisoo Shin; Baofang Cui; Kisuk Yang; Yi Sun Choi; Nakwon Choi; Soo Hyun Lee; Jae-Hyun Lee; Yong-Sun Bahn; Seung-Woo Cho
Publication Date
2021-08
Journal
NATURE BIOMEDICAL ENGINEERING, v.5, no.8, pp.830 - 846
Publisher
Nature Research
Abstract
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.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
https://pr.ibs.re.kr/handle/8788114/11073
DOI
10.1038/s41551-021-00743-8
ISSN
2157-846X
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > 1. Journal Papers (저널논문)
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