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Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees

Background and Aims: Globally, liver diseases account for 2 million deaths per year. For those with advanced liver disease the only curative approach is liver transplantation. However, less than 10% of those in need get a liver transplant due to limited organ availability. To circumvent this challen...

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Autores principales: Gontran, Emilie, Loarca, Lorena, El Kassis, Cyrille, Bouzhir, Latifa, Ayollo, Dmitry, Mazari-Arrighi, Elsa, Fuchs, Alexandra, Dupuis-Williams, Pascale
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389215/
https://www.ncbi.nlm.nih.gov/pubmed/34436115
http://dx.doi.org/10.3390/bioengineering8080112
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author Gontran, Emilie
Loarca, Lorena
El Kassis, Cyrille
Bouzhir, Latifa
Ayollo, Dmitry
Mazari-Arrighi, Elsa
Fuchs, Alexandra
Dupuis-Williams, Pascale
author_facet Gontran, Emilie
Loarca, Lorena
El Kassis, Cyrille
Bouzhir, Latifa
Ayollo, Dmitry
Mazari-Arrighi, Elsa
Fuchs, Alexandra
Dupuis-Williams, Pascale
author_sort Gontran, Emilie
collection PubMed
description Background and Aims: Globally, liver diseases account for 2 million deaths per year. For those with advanced liver disease the only curative approach is liver transplantation. However, less than 10% of those in need get a liver transplant due to limited organ availability. To circumvent this challenge, there has been a great focus in generating a bioengineered liver. Despite its essential role in liver functions, a functional biliary system has not yet been developed. In this framework, exploration of epithelial cell self-organogenesis and microengineering-driven geometrical cell confinement allow to envision the bioengineering of a functional biomimetic intrahepatic biliary tract. Approach: three-dimensional (3D) bile ducts were built in vitro by restricting cell adhesion to two-dimensional (2D) patterns to guide cell self-organization. Tree shapes mimicking the configuration of the human biliary system were micropatterned on glass slides, restricting cell attachment to these areas. Different tree geometries and culture conditions were explored to stimulate self-organogenesis of normal rat cholangiocytes (NRCs) used as a biliary cell model, either alone or in co-culture with human umbilical endothelial cells (HUVECs). Results: Pre-seeding the micropatterns with HUVECs promoted luminogenesis with higher efficiency to yield functional branched biliary tubes. Lumen formation, apico-basal polarity, and preservation of the cholangiocyte phenotype were confirmed. Moreover, intact and functional biliary structures were detached from the micropatterns for further manipulation. Conclusion: This study presents physiologically relevant 3D biliary duct networks built in vitro from 2D micropatterns. This opens opportunities for investigating bile duct organogenesis, physiopathology, and drug testing.
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spelling pubmed-83892152021-08-27 Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees Gontran, Emilie Loarca, Lorena El Kassis, Cyrille Bouzhir, Latifa Ayollo, Dmitry Mazari-Arrighi, Elsa Fuchs, Alexandra Dupuis-Williams, Pascale Bioengineering (Basel) Article Background and Aims: Globally, liver diseases account for 2 million deaths per year. For those with advanced liver disease the only curative approach is liver transplantation. However, less than 10% of those in need get a liver transplant due to limited organ availability. To circumvent this challenge, there has been a great focus in generating a bioengineered liver. Despite its essential role in liver functions, a functional biliary system has not yet been developed. In this framework, exploration of epithelial cell self-organogenesis and microengineering-driven geometrical cell confinement allow to envision the bioengineering of a functional biomimetic intrahepatic biliary tract. Approach: three-dimensional (3D) bile ducts were built in vitro by restricting cell adhesion to two-dimensional (2D) patterns to guide cell self-organization. Tree shapes mimicking the configuration of the human biliary system were micropatterned on glass slides, restricting cell attachment to these areas. Different tree geometries and culture conditions were explored to stimulate self-organogenesis of normal rat cholangiocytes (NRCs) used as a biliary cell model, either alone or in co-culture with human umbilical endothelial cells (HUVECs). Results: Pre-seeding the micropatterns with HUVECs promoted luminogenesis with higher efficiency to yield functional branched biliary tubes. Lumen formation, apico-basal polarity, and preservation of the cholangiocyte phenotype were confirmed. Moreover, intact and functional biliary structures were detached from the micropatterns for further manipulation. Conclusion: This study presents physiologically relevant 3D biliary duct networks built in vitro from 2D micropatterns. This opens opportunities for investigating bile duct organogenesis, physiopathology, and drug testing. MDPI 2021-08-05 /pmc/articles/PMC8389215/ /pubmed/34436115 http://dx.doi.org/10.3390/bioengineering8080112 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gontran, Emilie
Loarca, Lorena
El Kassis, Cyrille
Bouzhir, Latifa
Ayollo, Dmitry
Mazari-Arrighi, Elsa
Fuchs, Alexandra
Dupuis-Williams, Pascale
Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees
title Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees
title_full Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees
title_fullStr Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees
title_full_unstemmed Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees
title_short Self-Organogenesis from 2D Micropatterns to 3D Biomimetic Biliary Trees
title_sort self-organogenesis from 2d micropatterns to 3d biomimetic biliary trees
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389215/
https://www.ncbi.nlm.nih.gov/pubmed/34436115
http://dx.doi.org/10.3390/bioengineering8080112
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