The Strategic Use of Animal Models in Translational Research

Animal models are widely used in pulmonary research, but their relationship to human disease remains uncertain. In many cases, the morphological changes associated with a particular model may resemble those seen in human disease, but the corresponding biochemical events' nature and timeframe may differ. Nevertheless, gaining insight into human disease mechanisms may be possible by employing experimental approaches that minimize the problems associated with extrapolating data from animal studies. Such strategies may include using more than one model of a particular disease, employing different routes of administration of the injurious agent, using a variety of animal strains or species, or focusing on biochemical mechanisms common to both the animal model and its human counterpart. This last strategy is particularly useful in testing potential therapeutic agents or developing biomarkers for human lung disease. For example, we have utilized animal models of emphysema that specifically involve significant elastic fiber injury because the breakdown of these fibers is a critical component of the human disease. As a result, we developed a therapeutic approach to mitigating elastic fiber injury that may slow the progression of human pulmonary emphysema. The same models were also useful in testing a new biomarker for the disease that may be a better indicator of the efficacy of novel therapeutic agents. Thus, the appropriate use of animal models is critically important in translating experimental findings to the clinical setting.