Experimental liver fibrosis research: update on animal models, legal issues and translational aspects

TLDR

Liver fibrosis results from excessive extracellular matrix deposition driven by hepatic stellate cells and other liver cells, and the adoption of new EU animal welfare rules in 2013 is accelerating the need for optimized experimental protocols and better international communication. The review updates current animal models, techniques, and pathomechanisms, discusses complications and translational examples, and urges the international community to standardize models to meet legal requirements for replacement, refinement, and reduction. The authors review in vitro and in vivo animal studies, detailing current models and techniques to investigate hepatic stellate cell–mediated fibrosis. The review highlights complications in experimental liver fibrosis and illustrates how model findings can be translated to human disease and therapy.

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.