Preclinical models of lymphatic disease: the potential for growth factor and gene therapy

The human disease states that are characterized by functional lymphatic insufficiency currently lack a cure. Molecular approaches may ultimately provide a therapeutic window to reverse the stigmata of both primary and secondary lymphatic insufficiency. To harness the potential therapeutic power of lymphangiogenesis, testing the safety and efficacy of the treatment response will be necessary. This, in turn, necessitates the availability of suitable preclinical animal models of the disease processes in question, along with suitable research tools to permit an assessment of the response to applied therapies. An ideal model would reproducibly and inexpensively replicate the untreated disease of human lymphedema. It would closely simulate the biology, as we understand it, of the human disease, and would replicate both the pathogenesis of the disease, including its natural history and the temporal patterns of its clinical expression. In this way, one might aspire to make valid predictions about the human applicability of therapy by extrapolation from observations in animal models. In addition to the availability of suitable animal models, the required investigative tools must also be available. In the context of lymphangiogenesis, to assess the therapeutic response, one must certainly possess the ability to recognize newly developed lymphatic vasculature. Sophisticated immunohistochemical and imaging techniques make this increasingly feasible. Initial experimental observations indicate that growth factor and gene therapy with VEGF-C holds promise for the treatment of both primary and secondary forms of lymphedema.