期刊
VIRUSES-BASEL
卷 13, 期 5, 页码 -出版社
MDPI
DOI: 10.3390/v13050773
关键词
liver; hepatocytes; viral hepatitis; Plasmodium; hepatotropic pathogens; 3D cell models; in vitro; disease models; bioengineering tools; host– pathogen interactions; drug development
类别
资金
- Fundacao para a Ciencia e Tecnologia, Portugal [PD/BD/128371/2017]
- Fundacao para a Ciencia e Tecnologia (FCT)/Ministerio da Ciencia e do Ensino Superior (MCTES) [UIDB/04462/2020]
- FEDER under the PT2020 Partnership Agreement
- The Discoveries Centre for Regenerative and Precision Medicine (European Commission Horizon 2020 Research and Innovation programme) [739572]
- Fundação para a Ciência e a Tecnologia [PD/BD/128371/2017] Funding Source: FCT
Hepatitis viruses and liver-stage malaria are major liver infections causing high morbidity and mortality worldwide. The development of disease models for studying infection is hindered by the limited tropism of major human hepatotropic pathogens. Bioengineered cell models exhibit better performance in simulating the human liver microenvironment compared to conventional two-dimensional cell models, and are crucial for drug development and understanding the molecular mechanisms of infection.
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 Plasmodium falciparum and Plasmodium vivax 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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