Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications

Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro...

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Autores: Ortega Ribera, Martí, Fernández Iglesias, Anabel, Illa, Xavi, Moya, Ana, Molina, Víctor, Maeso Díaz, Raquel, Fondevila Campo, Constantino, Peralta Uroz, Carmen, Bosch i Genover, Jaume, Villa, Rosa, Gracia Sancho, Jordi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/132002
Acceso en línea:https://hdl.handle.net/2445/132002
Access Level:acceso abierto
Palabra clave:Cèl·lules hepàtiques
Malalties del fetge
Liver cells
Liver diseases
id ES_593f33de0ce1be4b15fc8a9987c1dbe3
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spelling Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applicationsOrtega Ribera, MartíFernández Iglesias, AnabelIlla, XaviMoya, AnaMolina, VíctorMaeso Díaz, RaquelFondevila Campo, ConstantinoPeralta Uroz, CarmenBosch i Genover, JaumeVilla, RosaGracia Sancho, JordiCèl·lules hepàtiquesMalalties del fetgeLiver cellsLiver diseasesMaintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver-resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver-resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.Wiley2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/132002Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1002/bit.26776Biotechnology and Bioengineering, 2018, vol. 115, num. 10, p. 2585-2594https://doi.org/10.1002/bit.26776cc-by (c) Ortega et al., 2018http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1320022026-05-27T06:46:51Z
dc.title.none.fl_str_mv Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
title Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
spellingShingle Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
Ortega Ribera, Martí
Cèl·lules hepàtiques
Malalties del fetge
Liver cells
Liver diseases
title_short Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
title_full Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
title_fullStr Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
title_full_unstemmed Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
title_sort Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications
dc.creator.none.fl_str_mv Ortega Ribera, Martí
Fernández Iglesias, Anabel
Illa, Xavi
Moya, Ana
Molina, Víctor
Maeso Díaz, Raquel
Fondevila Campo, Constantino
Peralta Uroz, Carmen
Bosch i Genover, Jaume
Villa, Rosa
Gracia Sancho, Jordi
author Ortega Ribera, Martí
author_facet Ortega Ribera, Martí
Fernández Iglesias, Anabel
Illa, Xavi
Moya, Ana
Molina, Víctor
Maeso Díaz, Raquel
Fondevila Campo, Constantino
Peralta Uroz, Carmen
Bosch i Genover, Jaume
Villa, Rosa
Gracia Sancho, Jordi
author_role author
author2 Fernández Iglesias, Anabel
Illa, Xavi
Moya, Ana
Molina, Víctor
Maeso Díaz, Raquel
Fondevila Campo, Constantino
Peralta Uroz, Carmen
Bosch i Genover, Jaume
Villa, Rosa
Gracia Sancho, Jordi
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules hepàtiques
Malalties del fetge
Liver cells
Liver diseases
topic Cèl·lules hepàtiques
Malalties del fetge
Liver cells
Liver diseases
description Maintenance of the complex phenotype of primary hepatocytes in vitro represents a limitation for developing liver support systems and reliable tools for biomedical research and drug screening. We herein aimed at developing a biosystem able to preserve human and rodent hepatocytes phenotype in vitro based on the main characteristics of the liver sinusoid: unique cellular architecture, endothelial biodynamic stimulation, and parenchymal zonation. Primary hepatocytes and liver sinusoidal endothelial cells (LSEC) were isolated from control and cirrhotic human or control rat livers and cultured in conventional in vitro platforms or within our liver-resembling device. Hepatocytes phenotype, function, and response to hepatotoxic drugs were analyzed. Results evidenced that mimicking the in vivo sinusoidal environment within our biosystem, primary human and rat hepatocytes cocultured with functional LSEC maintained morphology and showed high albumin and urea production, enhanced cytochrome P450 family 3 subfamily A member 4 (CYP3A4) activity, and maintained expression of hepatocyte nuclear factor 4 alpha (hnf4α) and transporters, showing delayed hepatocyte dedifferentiation. In addition, differentiated hepatocytes cultured within this liver-resembling device responded to acute treatment with known hepatotoxic drugs significantly different from those seen in conventional culture platforms. In conclusion, this study describes a new bioengineered device that mimics the human sinusoid in vitro, representing a novel method to study liver diseases and toxicology.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/132002
url https://hdl.handle.net/2445/132002
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1002/bit.26776
Biotechnology and Bioengineering, 2018, vol. 115, num. 10, p. 2585-2594
https://doi.org/10.1002/bit.26776
dc.rights.none.fl_str_mv cc-by (c) Ortega et al., 2018
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ortega et al., 2018
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300719

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