Animal models for the study of lymphatic insufficiency

Lymphedema is the term commonly employed to describe the spectrum of pathological states that arise as a consequence of functional lymphatic insufficiency. These human disease entities currently lack an effective cure. Satisfactory therapeutic strategies for both primary and secondary lymphedema will require additional insight into the complex cellular mechanisms and responses that comprise both normal lymphatic function and its regional derangement in states of pathologic dysfunction. Such insights must, initially, be derived from suitable animal models of the chronic human disease process. Historically, efforts to replicate the untreated disease of human lymphedema in animals, through surgery, irradiation, and toxicology, have been fraught with difficulty. The major impediments to the creation of satisfactory animal models have included an inability to reproduce the chronic disease in a stable, reproducible format. Recently, with the promise of potentially successful growth factor-mediated therapeutic lymphangiogenesis, and with the enhanced availability of investigative tools to assess therapeutic responses to molecular therapies, there has been a resurgence of interest in the development of viable animal models of lymphatic insufficiency. Current research has led to the development of genetic and postsurgical models of lymphedema that closely simulate the human conditions of primary and secondary lymphatic insufficiency, respectively. Such models will help to refine the assessment of various therapeutic approaches and their potential applicability to human disease interventions.