Applying the 3Rs to Liver Fibrosis research

This project aims to reduce and refine the use of mice in two aspects of liver fibrosis research. Bile-duct ligation, a common surgical technique for generating periportal liver fibrosis in animals, often gives rise to a high level of mortality. By using the chemical methapyrilene to cause periportal liver damage instead, the severity classification of the procedure under the Animals (Scientific Procedures) Act 1986 (ASPA) could be refined, from 'substantial' to 'moderate'. In addition, the project will investigate realtime imaging of the progression of liver fibrosis, using antibodies to detect myofibroblasts (the fibrosis-causing cells of the liver). This will allow repeated readouts from the same animal to be taken, thus reducing the numbers of animals used.

Liver disease is a major killer and one of the few major diseases predicted to rise in the future because of obesity and viral infections. Finding treatments requires the use of animals because several different cell types and several tissues combine to produce the main disease outcome - fibrosis or tissue scarring. This project will develop an animal model to test treatments that is less severe than the currently used surgical model. The project will also develop a way to image fibrosis using a novel antibody system developed by the applicants, so that fibrosis severity can be determined in live animals. By developing these refinements, the project will replace more severe procedures and reduce the numbers of animals required in liver disease research.