Clinical Relevance of Animal Models of Lymphatic Dysfunction and Lymphedema

Lymphedema is a chronic progressive condition, and treatment options are limited to physical therapy or surgical intervention, underscoring the need to develop preventative strategies. To do so, we must first understand the underlying mechanisms that contribute to the development of clinical lymphedema, which can be caused by a myriad of factors, including genetic mutations, infectious agents, and cancer treatments. Animal models are essential to study the pathogenesis of clinical lymphedema and to develop therapeutic interventions. Many animal models mimic the various aspects of lymphatic dysfunction and lymphedema seen in humans, and some species better represent different aspects or causes of lymphedema. However, no single model perfectly recapitulates human disease in a cost- and time-efficient manner; therefore, findings should be verified in multiple models and multiple species. In doing so, researchers will increase the likelihood of collecting rigorous, reliable data that could be effectively and efficiently translated into the clinic. This review explores genetic, infectious, and surgical animal models of lymphatic dysfunction and lymphedema and describes how these models can be used to understand clinical forms of lymphedema. Collectively, this information can provide valuable insight for the translational study of lymphatic diseases.