Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism
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 surro...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-03-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fbioe.2020.00163/full |
| _version_ | 1818311797067743232 |
|---|---|
| author | Vincenza De Gregorio Vincenza De Gregorio Mariarosaria Telesco Brunella Corrado Valerio Rosiello Francesco Urciuolo Paolo A. Netti Paolo A. Netti Paolo A. Netti Giorgia Imparato |
| author_facet | Vincenza De Gregorio Vincenza De Gregorio Mariarosaria Telesco Brunella Corrado Valerio Rosiello Francesco Urciuolo Paolo A. Netti Paolo A. Netti Paolo A. Netti Giorgia Imparato |
| author_sort | Vincenza De Gregorio |
| collection | DOAJ |
| description | 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-μTPs) 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. |
| first_indexed | 2024-12-13T08:07:40Z |
| format | Article |
| id | doaj.art-bcb4e8631a544bb194052d3f370c67ad |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-13T08:07:40Z |
| publishDate | 2020-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-bcb4e8631a544bb194052d3f370c67ad2022-12-21T23:54:17ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-03-01810.3389/fbioe.2020.00163515636Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass MetabolismVincenza De Gregorio0Vincenza De Gregorio1Mariarosaria Telesco2Brunella Corrado3Valerio Rosiello4Francesco Urciuolo5Paolo A. Netti6Paolo A. Netti7Paolo A. Netti8Giorgia Imparato9Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Naples, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, ItalyCenter for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Naples, ItalyCenter for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Naples, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, ItalyCenter for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Naples, ItalyInterdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Naples, ItalyDepartment of Chemical, Materials and Industrial Production Engineering (DICMAPI) University of Naples Federico II, Naples, ItalyCenter for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Naples, ItalyIntestine-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-μTPs) 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.https://www.frontiersin.org/article/10.3389/fbioe.2020.00163/fullfirst-pass metabolism of ethanol (Et-OH)intestine-liver-on-chipbottom-up tissue engineering approachendogenous ECM3D tissue |
| spellingShingle | Vincenza De Gregorio Vincenza De Gregorio Mariarosaria Telesco Brunella Corrado Valerio Rosiello Francesco Urciuolo Paolo A. Netti Paolo A. Netti Paolo A. Netti Giorgia Imparato Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism Frontiers in Bioengineering and Biotechnology first-pass metabolism of ethanol (Et-OH) intestine-liver-on-chip bottom-up tissue engineering approach endogenous ECM 3D tissue |
| title | Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism |
| title_full | Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism |
| title_fullStr | Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism |
| title_full_unstemmed | Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism |
| title_short | Intestine-Liver Axis On-Chip Reveals the Intestinal Protective Role on Hepatic Damage by Emulating Ethanol First-Pass Metabolism |
| title_sort | intestine liver axis on chip reveals the intestinal protective role on hepatic damage by emulating ethanol first pass metabolism |
| topic | first-pass metabolism of ethanol (Et-OH) intestine-liver-on-chip bottom-up tissue engineering approach endogenous ECM 3D tissue |
| url | https://www.frontiersin.org/article/10.3389/fbioe.2020.00163/full |
| work_keys_str_mv | AT vincenzadegregorio intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT vincenzadegregorio intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT mariarosariatelesco intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT brunellacorrado intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT valeriorosiello intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT francescourciuolo intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT paoloanetti intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT paoloanetti intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT paoloanetti intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism AT giorgiaimparato intestineliveraxisonchiprevealstheintestinalprotectiveroleonhepaticdamagebyemulatingethanolfirstpassmetabolism |