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

Artificial OrgansVolume 42, Issue 12 p. 1196-1205 Main Text Article A Biomimetic Human Gut-on-a-Chip for Modeling Drug Metabolism in Intestine Yaqiong Guo, Yaqiong Guo Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian School of Future Technology, University of Chinese Academy of Sciences, BeijingSearch for more papers by this authorZhongyu Li, Zhongyu Li Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, DalianSearch for more papers by this authorWentao Su, Wentao Su Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, DalianSearch for more papers by this authorLi Wang, Li Wang Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, DalianSearch for more papers by this authorYujuan Zhu, Yujuan Zhu Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian School of Future Technology, University of Chinese Academy of Sciences, BeijingSearch for more papers by this authorJianhua Qin, Corresponding Author Jianhua Qin jhqin@dicp.ac.cn orcid.org/0000-0001-5735-6436 Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian School of Future Technology, University of Chinese Academy of Sciences, Beijing CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, ChinaAddress correspondence and reprint requests to Jianhua Qin, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, 116023, Dalian, Liaoning, China. E-mail: jhqin@dicp.ac.cnSearch for more papers by this author Yaqiong Guo, Yaqiong Guo Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian School of Future Technology, University of Chinese Academy of Sciences, BeijingSearch for more papers by this authorZhongyu Li, Zhongyu Li Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, DalianSearch for more papers by this authorWentao Su, Wentao Su Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, DalianSearch for more papers by this authorLi Wang, Li Wang Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, DalianSearch for more papers by this authorYujuan Zhu, Yujuan Zhu Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian School of Future Technology, University of Chinese Academy of Sciences, BeijingSearch for more papers by this authorJianhua Qin, Corresponding Author Jianhua Qin jhqin@dicp.ac.cn orcid.org/0000-0001-5735-6436 Division of Biotechnology, CAS Key Laboratory of Separation Sciences for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian School of Future Technology, University of Chinese Academy of Sciences, Beijing CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, ChinaAddress correspondence and reprint requests to Jianhua Qin, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Zhongshan Road 457, 116023, Dalian, Liaoning, China. E-mail: jhqin@dicp.ac.cnSearch for more papers by this author First published: 05 September 2018 https://doi.org/10.1111/aor.13163Citations: 39Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract 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. Conflict of Interest The authors have declared no conflicts of interest for this article. Citing Literature Volume42, Issue12Special Issue: IFAO Review of Worldwide Survival Differences in HemodialysisDecember 2018Pages 1196-1205 RelatedInformation