DICP OpenIR
A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine
Guo, Yaqiong1,2; Li, Zhongyu1; Su, Wentao1; Wang, Li1; Zhu, Yujuan1,2; Qin, Jianhua1,2,3
Corresponding AuthorQin, Jianhua(jhqin@dicp.ac.cn)
KeywordGut-on-a-chip Caco-2 Intestinal metabolism Biomimetic Drug metabolism
Source PublicationARTIFICIAL ORGANS
2018-12-01
ISSN0160-564X
DOI10.1111/aor.13163
Volume42Issue:12Pages:1196-1205
Funding ProjectStrategic 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]
Funding OrganizationStrategic 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
WOS SubjectEngineering, Biomedical ; Transplantation
WOS Research AreaEngineering ; Transplantation
WOS KeywordCELL-LINE CACO-2 ; CARDIAC TISSUES ; PERMEABILITY ; VERAPAMIL ; ABSORPTION ; INDUCTION ; SYSTEM ; VILLIN
AbstractDrug 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.
Language英语
Funding OrganizationStrategic 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
WOS IDWOS:000454127100016
PublisherWILEY
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/166455
Collection中国科学院大连化学物理研究所
Corresponding AuthorQin, Jianhua
Affiliation1.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, CAS Key Lab Separat Sci Analyt Chem, Dalian, Peoples R China
2.Univ Chinese Acad Sci, Sch Future Technol, Beijing, Peoples R China
3.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China
Recommended Citation
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.
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