Issue 16, 2024

SARS-CoV-2-induced disruption of a vascular bed in a microphysiological system caused by type-I interferon from bronchial organoids

Abstract

Blood vessels show various COVID-19-related conditions including thrombosis and cytokine propagation. Existing in vitro blood vessel models cannot represent the consequent changes in the vascular structure or determine the initial infection site, making it difficult to evaluate how epithelial and endothelial tissues are damaged. Here, we developed a microphysiological system (MPS) that co-culture the bronchial organoids and the vascular bed to analyze infection site and interactions. In this system, virus-infected organoids caused damage in vascular structure. However, vasculature was not damaged or infected when the virus was directly introduced to vascular bed. The knockout of interferon-related genes and inhibition of the JAK/STAT pathway reduced the vascular damage, indicating the protective effect of interferon response suppression. The results demonstrate selective infection of bronchial epithelial cells and vascular damage by cytokines and also indicate the applicability of MPS to investigate how the infection influences vascular structure and functions.

Graphical abstract: SARS-CoV-2-induced disruption of a vascular bed in a microphysiological system caused by type-I interferon from bronchial organoids

Supplementary files

Article information

Article type
Paper
Submitted
12 Sep 2023
Accepted
29 Dec 2023
First published
09 Jan 2024
This article is Open Access
Creative Commons BY license

Lab Chip, 2024,24, 3863-3879

SARS-CoV-2-induced disruption of a vascular bed in a microphysiological system caused by type-I interferon from bronchial organoids

K. Fujimoto, Y. Kameda, Y. Nagano, S. Deguchi, T. Yamamoto, R. P. Krol, P. Gee, Y. Matsumura, T. Okamoto, M. Nagao, K. Takayama and R. Yokokawa, Lab Chip, 2024, 24, 3863 DOI: 10.1039/D3LC00768E

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