Large animal models for translational biomedical research

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Large Animal Models for Translational Biomedical Research

The translation of novel discoveries from basic research to clinical application is a long, often inefficient and thus costly process. Accordingly, the process of drug development requires optimization both for economic and for ethical reasons, in order to provide patients with appropriate treatments in a reasonable time frame. Consequently, “Translational Medicine” became a top priority in national and international roadmaps of human health research. The „Critical Path Initiative” of the Food and Drug Administration (FDA) in the USA and the „Innovative Medicine Initiative (IMI)“ of the European Union are prominent examples.

Appropriate animal models for the evaluation of efficacy and safety of new drugs or therapeutic concepts are critical for the success of translational research. In this context rodent models are most widely used due to the possibility of genetic and environmental standardization, a broad spectrum of strains adapted to specific scientific problems, and their acceptance by the regulatory authorities. However, findings in rodent models do not always reflect the clinical situation. Thus, animal models mimicking human anatomy and physiology more closely are urgently required.  For instance, the International Society for Stem Cell Research recommends in its Guidelines for the Clinical Translation of Stem Cells, that stem cells therapies should also be tested in large animal models.

In this respect the pig is an excellent candidate. As monogastric omnivores pigs share many anatomical and physiological characteristics with humans. The excellent reproductive performance of the pig is ideal for a model organism. The first pig whole genome sequence and many other genomic resources will be available in the near future. Efficient and precise techniques for the genetic modification of pigs have been established, facilitating the generation of tailored disease models.

According to this principle we are currently generating and analyzing genetically modified pig models for diabetes research, cancer research, osteoporosis, cystic fibrosis and muscular dystrophy. In addition we are generating multi-transgenic pigs as organ donors for xenotransplantation.