Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model
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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 clinical observations in human sepsis. We therefore conclude that this human liver organoid model is a valuable tool to investigate sepsis-related liver dysfunction and subsequent immune cell-related tissue repair/remodeling processes.
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Macrophage and monocyte recruitment is vital in the pathogenesis of liver disease, as these cells secrete inflammatory mediators that aggravate hepatocyte injury and promote further HSC activation.
“Macrophage and monocyte recruitment is vital in the pathogenesis of liver disease, as these cells secrete inflammatory mediators that aggravate hepatocyte injury and promote further HSC activation (Gröger M, 2016).”
From A 3D bioengineered human liver for the study of acute and chronic drug-induced hepatotoxicity and fibrosis (2026) · cites this paper as Gröger M, 2016
The Discussion reports that recruited monocytes increased pro-inflammatory cytokine release, but appeared to dampen inflammation-induced hepatocellular dysfunction. The Results likewise report reduced cell-damage markers after monocyte invasion—the opposite of the claimed aggravation of hepatocyte injury. The paper describes HSCs secreting chemoattractants for macrophages, not recruited monocytes promoting HSC activation. (LLM, conf=0.86)
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- Authors
- Gröger, M., Rennert, K., Giszas, B., Weiß, E., Dinger, J., Funke, H., Kiehntopf, M., Peters, F. T., Lupp, A., Bauer, M., Claus, R. A., Huber, O., & Mosig, A. S.
- Affiliations
- Jena University Hospital (DE)
- Corresponding author
- Mosig, Alexander S.
- ORCID
- Venue
- Scientific Reports
- Published
- 2016-02-23
- Volume
- 6
- Issue
- 1
- Pages
- 21868-21868
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4763209
- OpenAlex
- W2301260083
- Cited by
- 60
- References
- 71
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 6 · 2016: 4
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-05-14)
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- TU Graz, Internationale Beziehungen und Mobilitätsprogramme
- Bundesministerium für Bildung und Forschung (01EO1002, FKZ 01EO1002)
- Thüringer Aufbaubank (2011 VF 0005)
- Universitätsklinikum Jena
- Bundesinstitut für Risikobewertung (1328-511)
- Ústav analytické chemie, Akademie Věd České Republiky
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- monocytes, inflammation, Toll-like receptor activation, cytokines, VE-cadherin, apolipoprotein B, endothelial barrier disruption, hepatocyte dysfunction, microfluidic biochips, tissue repair
- MeSH terms
- Multidrug Resistance-Associated Protein 2, Cadherin 5, Albumins, Apolipoproteins B, Capillaries, Cell Communication, Gene Expression Regulation, Humans, Inflammation, Lipopolysaccharides, Liver, Models, Biological, Monocytes, Organoids, Signal Transduction, Antigens, CD, Cadherins, Cytokines, Coculture Techniques, Hepatocytes, Multidrug Resistance-Associated Proteins, ATP-Binding Cassette, Sub-Family C Proteins, Endothelial Cells, Toll-Like Receptors, Lab-On-A-Chip Devices
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