Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model

Scientific Reports
Marko GrögerAlexander S Mosig

Abstract

Liver dysfunction is an early event in sepsis-related multi-organ failure. We here report the establishment and characterization of a microfluidically supported in vitro organoid model of the human liver sinusoid. The liver organoid is composed of vascular and hepatocyte cell layers integrating non-parenchymal cells closely reflecting tissue architecture and enables physiological cross-communication in a bio-inspired fashion. Inflammation-associated liver dysfunction was mimicked by stimulation with various agonists of toll-like receptors. TLR-stimulation induced the release of pro- and anti-inflammatory cytokines and diminished expression of endothelial VE-cadherin, hepatic MRP-2 transporter and apolipoprotein B (ApoB), resulting in an inflammation-related endothelial barrier disruption and hepatocellular dysfunction in the liver organoid. However, interaction of the liver organoid with human monocytes attenuated inflammation-related cell responses and restored MRP-2 transporter activity, ApoB expression and albumin/urea production. The cellular events observed in the liver organoid closely resembled pathophysiological responses in the well-established sepsis model of peritoneal contamination and infection (PCI) in mice and cl...Continue Reading

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Citations

Feb 12, 2017·Environmental Toxicology and Pharmacology·Ghada S El-TanboulyHassan A El-Kashef
Jan 23, 2020·Lab on a Chip·Norman C PetersonMatteo Di Piazza
Jul 4, 2017·Future Science OA·Julia RogalPeter Loskill
Oct 7, 2017·Advanced Healthcare Materials·Janna NawrothPeter Loskill
Jul 4, 2017·Future Science OA·Alexander S Mosig
Jan 20, 2019·Critical Care : the Official Journal of the Critical Care Forum·Wen-Kuang YuLorraine B Ware
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Apr 27, 2021·Frontiers in Cell and Developmental Biology·Mohi MiahMuzlifah Haniffa

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Methods Mentioned

BETA
flow cytometry
chips
chip
FCS
density gradient centrifugation

Software Mentioned

FACSDiva
GraphPad
FCAP Array V3
FlowJo X
GraphPad Prism
Analyst

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