Kim, Jin Lee, Kyung-Tae Lee, Jong Seung Shin, Jisoo Cui, Baofang Yang, Kisuk Choi, Yi Sun Choi, Nakwon Lee, Soo Hyun Lee, Jae-Hyun Bahn, Yong-Sun Cho, Seung-Woo 2024-01-19T14:03:12Z 2024-01-19T14:03:12Z 2021-10-21 2021-08 https://pubs.kist.re.kr/handle/201004/116645 A neurovascular-unit-on-a-chip with a functional blood-brain barrier recapitulates the neurotropism and barrier penetration of the most common pathogen causing fungal meningitis. 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. English NATURE PUBLISHING GROUP Fungal brain infection modelled in a human-neurovascular-unit-on-a-chip with a functional blood-brain barrier Article 10.1038/s41551-021-00743-8 1 Nature Biomedical Engineering, v.5, no.8, pp.830 - 846 Nature Biomedical Engineering 5 8 830 846 N scie scopus 000661366800002 2-s2.0-85108011567 Engineering, Biomedical Engineering Article NECROSIS-FACTOR-ALPHA IN-VITRO MODEL ENDOTHELIAL-CELLS CRYPTOCOCCUS-NEOFORMANS HYALURONIC-ACID P-GLYCOPROTEIN SHEAR-STRESS ANIMAL-MODELS SELF-RENEWAL STEM-CELLS