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SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip
Guo, YQ; Luo, RH; Wang, YQ; Deng, PW; Song, TZ; Zhang, M; Wang, P; Zhang, X; Cui, KL; Tao, TT; Li, ZY; Chen, WW; Zheng, YT; Qin, JH
2021
发表期刊SCIENCE BULLETIN
ISSN2095-9273
卷号66期号:8页码:783-793
摘要Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has become a global pandemic. Clinical evidence suggests that the intestine is another high-risk organ for SARS-CoV-2 infection besides the lungs. However, a model that can accurately reflect the response of the human intestine to the virus is still lacking. Here, we created an intestinal infection model on a chip that allows the recapitulation of human relevant intestinal pathophysiology induced by SARSCoV-2 at organ level. This microengineered gut-on-chip reconstitutes the key features of the intestinal epithelium-vascular endothelium barrier through the three-dimensional (3D) co-culture of human intestinal epithelial, mucin-secreting, and vascular endothelial cells under physiological fluid flow. The intestinal epithelium showed permissiveness for viral infection and obvious morphological changes with injury of intestinal villi, dispersed distribution of mucus-secreting cells, and reduced expression of tight junction (E-cadherin), indicating the destruction of the intestinal barrier integrity caused by virus. Moreover, the vascular endothelium exhibited abnormal cell morphology, with disrupted adherent junctions. Transcriptional analysis revealed abnormal RNA and protein metabolism, as well as activated immune responses in both epithelial and endothelial cells after viral infection (e.g., upregulated cytokine genes), which may contribute to the injury of the intestinal barrier associated with gastrointestinal symptoms. This human organ system can partially mirror intestinal barrier injury and the human response to viral infection, which is not possible in existing in vitro culture models. It provides a unique and rapid platform to accelerate COVID-19 research and develop novel therapies. ? 2020 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
收录类别sci
语种英语
文献类型期刊论文
条目标识符http://ir.kiz.ac.cn/handle/152453/13815
专题科研部门_分子免疫药理学(郑永唐)
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GB/T 7714
Guo, YQ,Luo, RH,Wang, YQ,et al. SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip[J]. SCIENCE BULLETIN,2021,66(8):783-793.
APA Guo, YQ.,Luo, RH.,Wang, YQ.,Deng, PW.,Song, TZ.,...&Qin, JH.(2021).SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip.SCIENCE BULLETIN,66(8),783-793.
MLA Guo, YQ,et al."SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip".SCIENCE BULLETIN 66.8(2021):783-793.
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