Experimental liver fibrosis research: update on animal models, legal issues and translational aspects
Christian Liedtke,Tom Luedde,Tilman Sauerbruch,D. Scholten,Konrad L. Streetz,Frank Tacke,Rene Tolba,Christian Trautwein,Jonel Trebicka,Ralf Weiskirchen +9 more
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TLDR
This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation.Abstract:
Liver fibrosis is defined as excessive extracellular matrix deposition and is based on complex interactions between matrix-producing hepatic stellate cells and an abundance of liver-resident and infiltrating cells. Investigation of these processes requires in vitro and in vivo experimental work in animals. However, the use of animals in translational research will be increasingly challenged, at least in countries of the European Union, because of the adoption of new animal welfare rules in 2013. These rules will create an urgent need for optimized standard operating procedures regarding animal experimentation and improved international communication in the liver fibrosis community. This review gives an update on current animal models, techniques and underlying pathomechanisms with the aim of fostering a critical discussion of the limitations and potential of up-to-date animal experimentation. We discuss potential complications in experimental liver fibrosis and provide examples of how the findings of studies in which these models are used can be translated to human disease and therapy. In this review, we want to motivate the international community to design more standardized animal models which might help to address the legally requested replacement, refinement and reduction of animals in fibrosis research.read more
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Targeting hepatic macrophages to treat liver diseases
TL;DR: Evidence from mouse models and early clinical studies in patients with non-alcoholic steatohepatitis and fibrosis support the notion that pathogenic macrophage subsets can be successfully translated into novel treatment options for patients with liver disease.
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Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis
Oliver Krenkel,Tobias Puengel,Olivier Govaere,Ali T. Abdallah,Jana C. Mossanen,Marlene Kohlhepp,Anke Liepelt,Eric Lefebvre,Tom Luedde,Claus Hellerbrand,Ralf Weiskirchen,Thomas Longerich,Ivan G. Costa,Quentin M. Anstee,Christian Trautwein,Frank Tacke +15 more
TL;DR: Pharmacological inhibition of CCR2+ monocyte recruitment efficiently ameliorates insulin resistance, hepatic inflammation, and fibrosis, corroborating the therapeutic potential of CVC in patients with NASH.
Journal ArticleDOI
Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis.
Carmen G. Tag,Sibille Sauer-Lehnen,Sabine Weiskirchen,Erawan Borkham-Kamphorst,Rene Tolba,Frank Tacke,Ralf Weiskirchen +6 more
TL;DR: A detailed surgical procedure is provided for the BDL model in mice that induce a highly reproducible fibrotic response in accordance to the 3R rule for animal welfare postulated by Russel and Burch in 1959.
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Experimental models of liver fibrosis
Sara Crespo Yanguas,Bruno Cogliati,Joost Willebrords,Michaël Maes,Isabelle Colle,Bert Van Den Bossche,Claudia P. Oliveira,Wellington Andraus,Venâncio Avancini Ferreira Alves,Isabelle Leclercq,Mathieu Vinken +10 more
TL;DR: A state-of-the-art overview of in vivo and in vitro models used in the field of experimental liver fibrosis research is provided.
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The carbon tetrachloride model in mice
TL;DR: A short series of standard operation procedures (SOPs) summarizing the most relevant and widely accepted experimental models for the induction of liver injury leading to liver fibrosis are presented, with the aim of reducing animal experimentation according to the 3R principle.
References
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