A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine

doi:10.1111/aor.13163

	A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine
	Guo, Yaqiong 1,2; Li, Zhongyu 2; Su, Wentao 2; Wang, Li 2; Zhu, Yujuan 1,2; Qin, Jianhua 1,2,3
刊名	ARTIFICIAL ORGANS
	2018-12-01
卷号	42 期号:12 页码:1196-1205
关键词	Gut-on-a-chip Caco-2 Intestinal metabolism Biomimetic Drug metabolism
ISSN号	0160-564X
DOI	10.1111/aor.13163
通讯作者	Qin, Jianhua(jhqin@dicp.ac.cn)
英文摘要	Drug metabolism in the intestine is considered to substantially contribute to the overall first-pass metabolism, which has been neglected for a long time. It is highly desirable to develop a reliable model to evaluate drug metabolism in the intestine in vitro. In this work, we made the first attempt to develop a biomimetic human gut-on-a-chip for modeling drug metabolism in intestine. In this chip, constant flow, together with porous nitrocellulose membrane and collagen I, mimics an in vivo-like intestinal microenvironment. The Caco-2 cells grown in the chip formed a compact intestinal epithelial layer with continuous expression of the tight junction protein, ZO-1. Furthermore, higher gene expression of villin, sucrase-isomaltase, and alkaline phosphatase demonstrated that cells in the biomimetic human gut-on-a-chip device were more mature with near-physiological functions compared to the control on planar substrate. In particular, cellular metabolic activity was assessed on different substrates, indicating higher metabolic efficiency of ifosfamide and verapamil in the biomimetic human gut-on-a-chip model. Taken together, our results suggested that this biomimetic human gut-on-a-chip promoted the differentiation of intestinal cells with enhanced functionality by creating a biomimetic 3D microenvironment in vitro. It might offer a bioactive, low-cost, and flexible in vitro platform for studies on intestinal metabolism as well as preclinical drug development.
资助项目	Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020900] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDPB0305] ; Key Program of the Chinese Academy of Sciences[KFZD-SW-213] ; International Science & Technology Cooperation Program of China[2015DFA00740] ; National Key R&D Program of China[2017YFB0405400] ; National Natural Science Foundation of China[91543121] ; National Natural Science Foundation of China[81573394] ; National Natural Science Foundation of China[31671038] ; National Natural Science Foundation of China[81603075] ; National Natural Science Foundation of China[21607151] ; National Natural Science Foundation of China[81703470] ; Innovation Program of Science and Research from the DICP, CAS[DICP TMSR201601]
WOS关键词	CELL-LINE CACO-2 ; CARDIAC TISSUES ; PERMEABILITY ; VERAPAMIL ; ABSORPTION ; INDUCTION ; SYSTEM ; VILLIN
WOS研究方向	Engineering ; Transplantation
语种	英语
出版者	WILEY
WOS记录号	WOS:000454127100016
资助机构	Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; International Science & Technology Cooperation Program of China ; International Science & Technology Cooperation Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS
内容类型	期刊论文
源URL	[http://cas-ir.dicp.ac.cn/handle/321008/166454]
专题	大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者	Qin, Jianhua
作者单位	1.Univ Chinese Acad Sci, Sch Future Technol, Beijing, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, CAS Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China 3.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Guo, Yaqiong,Li, Zhongyu,Su, Wentao,et al. A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine[J]. ARTIFICIAL ORGANS,2018,42(12):1196-1205.
APA	Guo, Yaqiong,Li, Zhongyu,Su, Wentao,Wang, Li,Zhu, Yujuan,&Qin, Jianhua.(2018).A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine.ARTIFICIAL ORGANS,42(12),1196-1205.
MLA	Guo, Yaqiong,et al."A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine".ARTIFICIAL ORGANS 42.12(2018):1196-1205.