Bioengineered Liver Cell Models of Hepatotropic Infections

Hepatitis viruses and liver-stage malaria are within the liver infections causing higher morbidity and mortality rates worldwide. The highly restricted tropism of the major human hepatotropic pathogens—namely, the human hepatitis B and C viruses and the <i>Plasmodium falciparum</i> and &...

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Main Authors: Francisca Arez, Ana F. Rodrigues, Catarina Brito, Paula M. Alves
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/13/5/773
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author Francisca Arez
Ana F. Rodrigues
Catarina Brito
Paula M. Alves
author_facet Francisca Arez
Ana F. Rodrigues
Catarina Brito
Paula M. Alves
author_sort Francisca Arez
collection DOAJ
description Hepatitis viruses and liver-stage malaria are within the liver infections causing higher morbidity and mortality rates worldwide. The highly restricted tropism of the major human hepatotropic pathogens—namely, the human hepatitis B and C viruses and the <i>Plasmodium falciparum</i> and <i>Plasmodium vivax</i> parasites—has hampered the development of disease models. These models are crucial for uncovering the molecular mechanisms underlying the biology of infection and governing host–pathogen interaction, as well as for fostering drug development. Bioengineered cell models better recapitulate the human liver microenvironment and extend hepatocyte viability and phenotype in vitro, when compared with conventional two-dimensional cell models. In this article, we review the bioengineering tools employed in the development of hepatic cell models for studying infection, with an emphasis on 3D cell culture strategies, and discuss how those tools contributed to the level of recapitulation attained in the different model layouts. Examples of host–pathogen interactions uncovered by engineered liver models and their usefulness in drug development are also presented. Finally, we address the current bottlenecks, trends, and prospect toward cell models’ reliability, robustness, and reproducibility.
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spelling doaj.art-72f4f2ebf57b412f81e7ff2a36a19fbd2023-11-21T17:26:49ZengMDPI AGViruses1999-49152021-04-0113577310.3390/v13050773Bioengineered Liver Cell Models of Hepatotropic InfectionsFrancisca Arez0Ana F. Rodrigues1Catarina Brito2Paula M. Alves3iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, PortugaliBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, 2781-901 Oeiras, PortugalHepatitis viruses and liver-stage malaria are within the liver infections causing higher morbidity and mortality rates worldwide. The highly restricted tropism of the major human hepatotropic pathogens—namely, the human hepatitis B and C viruses and the <i>Plasmodium falciparum</i> and <i>Plasmodium vivax</i> parasites—has hampered the development of disease models. These models are crucial for uncovering the molecular mechanisms underlying the biology of infection and governing host–pathogen interaction, as well as for fostering drug development. Bioengineered cell models better recapitulate the human liver microenvironment and extend hepatocyte viability and phenotype in vitro, when compared with conventional two-dimensional cell models. In this article, we review the bioengineering tools employed in the development of hepatic cell models for studying infection, with an emphasis on 3D cell culture strategies, and discuss how those tools contributed to the level of recapitulation attained in the different model layouts. Examples of host–pathogen interactions uncovered by engineered liver models and their usefulness in drug development are also presented. Finally, we address the current bottlenecks, trends, and prospect toward cell models’ reliability, robustness, and reproducibility.https://www.mdpi.com/1999-4915/13/5/773liverhepatocytesviral hepatitis<i>Plasmodium</i>hepatotropic pathogens3D cell models
spellingShingle Francisca Arez
Ana F. Rodrigues
Catarina Brito
Paula M. Alves
Bioengineered Liver Cell Models of Hepatotropic Infections
Viruses
liver
hepatocytes
viral hepatitis
<i>Plasmodium</i>
hepatotropic pathogens
3D cell models
title Bioengineered Liver Cell Models of Hepatotropic Infections
title_full Bioengineered Liver Cell Models of Hepatotropic Infections
title_fullStr Bioengineered Liver Cell Models of Hepatotropic Infections
title_full_unstemmed Bioengineered Liver Cell Models of Hepatotropic Infections
title_short Bioengineered Liver Cell Models of Hepatotropic Infections
title_sort bioengineered liver cell models of hepatotropic infections
topic liver
hepatocytes
viral hepatitis
<i>Plasmodium</i>
hepatotropic pathogens
3D cell models
url https://www.mdpi.com/1999-4915/13/5/773
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AT paulamalves bioengineeredlivercellmodelsofhepatotropicinfections