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DOI	10.1016/j.scib.2020.11.015
	SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip
	Guo Y.; Luo R.; Wang Y.; Deng P.; Song T.; Zhang M.; Wang P.; Zhang X.; Cui K.; Tao T.; Li Z.; Chen W.; Zheng Y.; Qin J.
发表日期	2021
ISSN	20959273
起始页码	783
结束页码	793
卷号	66 期号:8
英文摘要	Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-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 SARS-CoV-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
关键词	COVID-19 Gastrointestinal infection Microphysiological system Organ-on-a-chip SARS-CoV-2
英文关键词	Biomimetics; Endothelial cells; Flow of fluids; Viruses; Gastrointestinal symptoms; Intestinal epithelium; Morphological changes; Physiological fluids; Severe acute respiratory syndrome coronavirus; Threedimensional (3-d); Transcriptional analysis; Vascular endothelial cells; Diseases
语种	英语
来源期刊	Science Bulletin
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/207415
作者单位	CAS Key Laboratory of SSAC, Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China; Institute For Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Kunming National High-level Bio-safety Research Center for Non-human Primates, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650107, China; Key Laboratory of Animal Models and Human, Disease Mechanisms of Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China; KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China
推荐引用方式 GB/T 7714	Guo Y.,Luo R.,Wang Y.,et al. SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip[J],2021,66(8).
APA	Guo Y..,Luo R..,Wang Y..,Deng P..,Song T..,...&Qin J..(2021).SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip.Science Bulletin,66(8).
MLA	Guo Y.,et al."SARS-CoV-2 induced intestinal responses with a biomimetic human gut-on-chip".Science Bulletin 66.8(2021).