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HEPASPHER SIGNED

Mimicking liver disease and regeneration in vitro for drug development and liver transplantation

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EC-Contrib. €

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Project "HEPASPHER" data sheet

The following table provides information about the project.

Coordinator
KAROLINSKA INSTITUTET 

Organization address
address: Nobels Vag 5
city: STOCKHOLM
postcode: 17177
website: www.ki.se

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Sweden [SE]
 Total cost 2˙413˙449 €
 EC max contribution 2˙413˙449 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    KAROLINSKA INSTITUTET SE (STOCKHOLM) coordinator 2˙413˙449.00

Map

 Project objective

The liver is a vital organ for synthesis and detoxification. The most significant liver diseases are hepatitis, non alcoholic fatty liver disease (NAFLD), non-alcoholic fatty liver steatohepatitis (NASH), carcinoma and cirrhosis. An additional and important cause of liver injury is adverse drug reactions (ADRs). In particular NAFLD is the most common liver disease affecting between 20% and 44% of European adults and 43-70% of patients with type 2 diabetes, and is one prime cause for chronic and end-stage liver disease, such as cirrhosis and primary hepatocellular carcinoma. This proposal is based on recent findings in the laboratory: The development of novel 3D spheroid system with chemically defined media allowing studies of chronic drug toxicity, relevant liver disease and liver function for 5 weeks in vitro, the finding of the role of miRNA in hepatocyte dedifferentiation and that hepatocytes during spheroid formation first de-differentiate but later in spheroids re-differentiate to an in vivo relevant phenotype. This forms the basis for the main objectives: i) to study diseased liver in vitro with identification of mechanisms, biomarkers and novel drug candidates for treatment of NAFLD and fibrosis, ii) evaluate drug toxicity sensitivity and mechanisms in diseased liver systems and iii) further develop methods for hepatocyte proliferation and regeneration in vitro for transplantation purposes, including genetic editing in cases of hepatocytes obtained from patients with genetically inherited liver diseases.

This work is carried out in close contact with the Hepatology unit at the Karolinska Hospital partly using resources at the Science for Life Laboratory at Karolinska. It is anticipated that the project can provide with novel mechanisms, biomarkers and new targets for treatment of liver disease as well as novel methods for clinically applicable liver regeneration without the use of stem cells or transformed cells.

 Publications

year authors and title journal last update
List of publications.
2019 Volker M. Lauschke, Reza Zandi Shafagh, Delilah F. G. Hendriks, Magnus Ingelman‐Sundberg
3D primary hepatocyte culture systems for analyses of liver diseases, drug metabolism and toxicity: Emerging culture paradigms and applications
published pages: 1800347, ISSN: 1860-6768, DOI: 10.1002/biot.201800347
Biotechnology Journal 2019-05-22
2019 Volker M. Lauschke, Yitian Zhou, Magnus Ingelman-Sundberg
Novel genetic and epigenetic factors of importance for inter-individual differences in drug disposition, response and toxicity
published pages: , ISSN: 0163-7258, DOI: 10.1016/j.pharmthera.2019.01.002
Pharmacology & Therapeutics 2019-05-22
2018 Catherine C Bell, Anita C A Dankers, Volker M Lauschke, Rowena Sison-Young, Roz Jenkins, Cliff Rowe, Chris E Goldring, Kevin Park, Sophie L Regan, Tracy Walker, Chris Schofield, Audrey Baze, Alison J Foster, Dominic P Williams, Amy W M van de Ven, Frank Jacobs, Jos van Houdt, Tuula Lähteenmäki, Jan Snoeys, Satu Juhila, Lysiane Richert, Magnus Ingelman-Sundberg
Comparison of Hepatic 2D Sandwich Cultures and 3D Spheroids for Long-term Toxicity Applications: A Multicenter Study
published pages: 655-666, ISSN: 1096-6080, DOI: 10.1093/toxsci/kfx289
Toxicological Sciences 162/2 2019-05-22
2019 Isabel Cordero-Herrera, Mikael Kozyra, Zhengbing Zhuge, Sarah McCann Haworth, Chiara Moretti, Maria Peleli, Mayara Caldeira-Dias, Arghavan Jahandideh, Han Huirong, Josiane de Campos Cruz, Andrei L. Kleschyov, Marcelo F. Montenegro, Magnus Ingelman-Sundberg, Eddie Weitzberg, Jon O. Lundberg, Mattias Carlstrom
AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis
published pages: 217-226, ISSN: 0027-8424, DOI: 10.1073/pnas.1809406115
Proceedings of the National Academy of Sciences 116/1 2019-05-22
2018 Sabine U Vorrink, Yitian Zhou, Magnus Ingelman-Sundberg, Volker M Lauschke
Prediction of Drug-Induced Hepatotoxicity Using Long-Term Stable Primary Hepatic 3D Spheroid Cultures in Chemically Defined Conditions
published pages: 655-665, ISSN: 1096-6080, DOI: 10.1093/toxsci/kfy058
Toxicological Sciences 163/2 2019-05-22

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