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.
Highlights
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
The combination of various Matrix metalloproteinase (MMP) and Tissue inhibitor of metalloproteinase (TIMP) depends on the disease phases and results at later stages of liver injury in an expression pattern in which MFBs express a combination of MMPs that have the ability to degrade normal liver matrix while inhibiting degradation of the fibrillar collagens that accumulate in liver fibrosis [8]
We summarize current animal models that are in use and describe the mechanisms that underlie the formation of hepatic fibrogenesis
Summary
New international animal welfare rules will have a deep impact on fibrosis research, at least in the EU. Animal models are still the gold standard in fibrosis research. New, sophisticated transgenic approaches will allow investigation of specialized topics regarding fibrosis initiation, progression and resolution. Current data from these animal models prove that these findings are highly relevant and can be translated to the clinic. Competing interests All authors declare that they have no competing interests. Authors’ contributions RW coordinated the writing of this review, wrote sections of it and designed the figures. FT and KS wrote individual sections of this review and helped to arrange the figures. All authors read and approved the final manuscript. Authors’ information For the Transregional Collaborative Research Centre “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (SFB/TRR57)
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