Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism

被引:35
|
作者
De Gregorio, Vincenza [1 ,2 ]
Telesco, Mariarosaria [1 ]
Corrado, Brunella [1 ]
Rosiello, Valerio [2 ]
Urciuolo, Francesco [2 ]
Netti, Paolo A. [1 ,2 ,3 ]
Imparato, Giorgia [1 ]
机构
[1] Ist Italiano Tecnol, CRIB, Ctr Adv Biomat HealthCare, Naples, Italy
[2] Univ Naples Federico II, Interdisciplinay Res Ctr Biomat CRIB, Naples, Italy
[3] Univ Naples Federico II, Dept Chem Mat & Ind Prod Engn DICMAPI, Naples, Italy
关键词
first-pass metabolism of ethanol (Et-OH); intestine-liver-on-chip; bottom-up tissue engineering approach; endogenous ECM; 3D tissue; CELL-CULTURE; MICROPHYSIOLOGICAL SYSTEMS; IN-VITRO; DRUG; ALCOHOL; GUT; CONSUMPTION; MICROBIOME; EPITHELIUM; BARRIER;
D O I
10.3389/fbioe.2020.00163
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Intestine-Liver-on-chip systems can be useful to predict oral drug administration and first-pass metabolism in vitro in order to partly replace the animal model. While organ-on-chip technology can count on sophisticated micro-physiological devices, the engineered organs still remain artificial surrogates of the native counterparts. Here, we used a bottom-up tissue engineering strategy to build-up physiologically functional 3D Human Intestine Model (3D-HIM) as well as 3D Liver-microtissues (HepG2-mu TPs) in vitro and designed a microfluidic Intestine-Liver-On-Chip (InLiver-OC) to emulate first-pass mechanism occurring in vivo. Our results highlight the ethanol-induced 3D-HIM hyper-permeability and stromal injury, the intestinal prevention on the liver injury, as well as the synergic contribution of the two 3D tissue models on the release of metabolic enzymes after high amount of ethanol administration.
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页数:19
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