Animal Models for the Molecular and Mechanistic Study of Lymphatic Biology and Disease

Abstract

The development of animal model systems for the study of the lymphatic system has resulted in an explosion of information regarding the mechanisms governing lymphatic development and the diseases associated with lymphatic dysfunction. Animal studies have led to a new molecular model of embryonic lymphatic vascular development, and have provided insight into the pathophysiology of both inherited and acquired lymphatic insufficiency. It has become apparent, however, that the importance of the lymphatic system to human disease extends, beyond its role in lymphedema, to many other diverse pathologic processes, including, very notably, inflammation and tumor lymphangiogenesis. Here, we have undertaken a systematic review of the models as they relate to molecular and functional characterization of the development, maturation, genetics, heritable and acquired diseases, and neoplastic implications of the lymphatic system. The translation of these advances into therapies for human diseases associated with lymphatic dysfunction will require the continued study of the lymphatic system through robust animal disease models that simulate their human counterparts.

Lymphatic deletion of calcitonin receptor–like receptor exacerbates intestinal inflammation

“…This study introduces a nonsurgical model of systemic lymphatic vascular insufficiency, currently lacking in the field (46). Future studies with prolonged injury models, such as ischemia/reperfusion, irradiation, or dextran sodium sulfate-induced colitis, will be very informative.…”

Growth Factor Therapy and Autologous Lymph Node Transfer in Lymphedema

“…Most previous reports of growth factor therapy in lymphedema are based on mouse or rabbit models, which have several limitations when considering their clinical translation to the therapy of human patients. 12,15,16,19,25,26,27 First, the hydrostatic conditions are dramatically different in mice because humans are considerably taller. This also means that the absolute lymphatic area damaged in humans is greater, and the regenerating lymphatic vessels must span a longer distance to form anastomoses with both the distal and proximal ends of the lymphatic vascular tree.…”

Therapeutic Responses to Exogenous VEGF-C Administration in Experimental Lymphedema: Immunohistochemical and Molecular Characterization

“…3,25 While the ability of VEGF-C to augment post-natal lymphangiogenesis has not been universally observed, 9 both gene-and protein-mediated VEGF-C therapies seem potentially promising. [5][6][7]26 While the mechanism of the VEGF-C's therapeutic benefit cannot be definitively linked to well-established induction of new lymphatic vascular growth (therapeutic lymphangiogenesis), the ameliorative effect of VEGF-C augmentation is evident in the murine model under investigation.…”