liver disease

Details about this human disease

Synonyms (2)

disorder of liver (disorder), hepatic disorder


Definitions (0)

None defined


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LivSys Transfer - Transfer of the LivSys in vitro system for hepatotoxicity into application

The aim of this project is to validate and improve an in vitro test system developed in a previous project for the prediction of hepatotoxicity induced by chemical substances and drugs. For this purpose, the test system will be supplemented with immunological cells in order to be able to detect idiosyncratic reactions. In the subproject of the working group of Prof. Daniel Seehofer and Dr. Georg Damm, primary liver cells will be provided and the in vitro model will be improved by Kupffer cells.

Programme: This Project is not associated with a Programme

Public web page: Not specified

Start date: 1st Feb 2017

End date: 31st Dec 2020

In Vivo and In Vitro Characterization of Primary Human Liver Macrophages and Their Inflammatory State
LivSys Transfer - Transfer of the LivSys in vitro system for hepatotoxicity into application

Abstract (Expand)

Liver macrophages (LMs) play a central role in acute and chronic liver pathologies. Investigation of these processes in humans as well as the development of diagnostic tools and new therapeutic strategies … require in vitro models that closely resemble the in vivo situation. In our study, we sought to gain further insight into the role of LMs in different liver pathologies and into their characteristics after isolation from liver tissue. For this purpose, LMs were characterized in human liver tissue sections using immunohistochemistry and bioinformatic image analysis. Isolated cells were characterized in suspension using FACS analyses and in culture using immunofluorescence staining and laser scanning microscopy as well as functional assays. The majority of our investigated liver tissues were characterized by anti-inflammatory LMs which showed a homogeneous distribution and increased cell numbers in correlation with chronic liver injuries. In contrast, pro-inflammatory LMs appeared as temporary and locally restricted reactions. Detailed characterization of isolated macrophages revealed a complex disease dependent pattern of LMs consisting of pro- and anti-inflammatory macrophages of different origins, regulatory macrophages and monocytes. Our study showed that in most cases the macrophage pattern can be transferred in adherent cultures. The observed exceptions were restricted to LMs with pro-inflammatory characteristics.

Authors: Andrea Zimmermann, René Hänsel, Kilian Gemünden, Victoria Kegel-Hübner, Jonas Babel, Hendrik Bläker, Madlen Matz-Soja, Daniel Seehofer, Georg Damm

Date Published: 1st Apr 2021

Publication Type: Journal article

Human Diseases: liver disease, liver cancer

Multilineage communication regulates human liver bud development from pluripotency.
Leipzig Melanoma Studies

Abstract (Expand)

Conventional two-dimensional differentiation from pluripotency fails to recapitulate cell interactions occurring during organogenesis. Three-dimensional organoids generate complex organ-like tissues; … however, it is unclear how heterotypic interactions affect lineage identity. Here we use single-cell RNA sequencing to reconstruct hepatocyte-like lineage progression from pluripotency in two-dimensional culture. We then derive three-dimensional liver bud organoids by reconstituting hepatic, stromal, and endothelial interactions, and deconstruct heterogeneity during liver bud development. We find that liver bud hepatoblasts diverge from the two-dimensional lineage, and express epithelial migration signatures characteristic of organ budding. We benchmark three-dimensional liver buds against fetal and adult human liver single-cell RNA sequencing data, and find a striking correspondence between the three-dimensional liver bud and fetal liver cells. We use a receptor-ligand pairing analysis and a high-throughput inhibitor assay to interrogate signalling in liver buds, and show that vascular endothelial growth factor (VEGF) crosstalk potentiates endothelial network formation and hepatoblast differentiation. Our molecular dissection reveals interlineage communication regulating organoid development, and illuminates previously inaccessible aspects of human liver development.

Authors: J. G. Camp, K. Sekine, T. Gerber, H. Loeffler-Wirth, H. Binder, M. Gac, S. Kanton, J. Kageyama, G. Damm, D. Seehofer, L. Belicova, M. Bickle, R. Barsacchi, R. Okuda, E. Yoshizawa, M. Kimura, H. Ayabe, H. Taniguchi, T. Takebe, B. Treutlein

Date Published: 22nd Jun 2017

Publication Type: Not specified

Human Diseases: liver disease

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