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

Ortega-Ribera, Martí; Fernández-Iglesias, Anabel; Illa, Xavi; Moya, Ana; Molina, Víctor; Maeso-Díaz, Raquel; Fondevila, Constantino; Peralta, Carmen; Bosch, Jaime; Villa, Rosa; Gracia Sancho, Jorge Sergio (2018). Resemblance of the human liver sinusoid in a fluidic device with biomedical and pharmaceutical applications. Biotechnology and bioengineering, 115(10), pp. 2585-2594. Wiley 10.1002/bit.26776

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine > Hepatology
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Visceral Surgery and Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Hepatologie

UniBE Contributor:

Bosch, Jaime and Gracia Sancho, Jorge Sergio

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1097-0290

Publisher:

Wiley

Language:

English

Submitter:

Thi Thao Anh Pham

Date Deposited:

17 Dec 2018 10:35

Last Modified:

23 Oct 2019 17:29

Publisher DOI:

10.1002/bit.26776

PubMed ID:

29940068

Uncontrolled Keywords:

LSEC hepatocyte liver sinusoidal endothelial cells liver-on-a-chip sinusoid

BORIS DOI:

10.7892/boris.122123

URI:

https://boris.unibe.ch/id/eprint/122123

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