期刊
ARTIFICIAL ORGANS
卷 42, 期 12, 页码 1196-1205出版社
WILEY
DOI: 10.1111/aor.13163
关键词
Gut-on-a-chip; Caco-2; Intestinal metabolism; Biomimetic; Drug metabolism
资金
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16020900, 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, 81573394, 31671038, 81603075, 21607151, 81703470]
- Innovation Program of Science and Research from the DICP, CAS [DICP TMSR201601]
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.
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