Modified Mouse Models of Chronic Secondary Lymphedema: Tail and Hind Limb Models

• Authors: Heungman Jun, Korea University; Ji Yoon Lee, Yonsei University; Ji Hun Kim, University of Ulsan; Minsu Noh, Asan Medical Center; Tae-Won Kwon, Asan Medical Center; Yong-Pil Cho Cho, Asan Medical Center; Young-sup Yoon, Emory University
• Journal Title: ANNALS OF VASCULAR SURGERY
• Volume: Volume 43
• Publisher: ELSEVIER SCIENCE INC | 2017-08-01, Pages 288-295
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.avsg.2017.01.023
• Subjects: Health Sciences, Medicine and Surgery; Engineering, Biomedical
• Keywords: Science & Technology; Life Sciences & Biomedicine; Surgery; Peripheral Vascular Disease; Cardiovascular System & Cardiology; LYMPHANGIOSARCOMA; THERAPY; DISEASE

Abstract

Background Postsurgical secondary lymphedema is usually a progressive and lifelong condition lacking any curative treatment. The aim of this study was to develop new, simple surgical mouse models of chronic lymphedema, better simulating chronic nature of human postsurgical lymphedema. Methods Two experimental mouse models of secondary lymphedema were created surgically without radiation by modifications of the previously described methods: the tail model and the hind limb model. Lymphedema formation was clinically assessed and quantitatively evaluated by measuring circumferences and limb volumes. Postmortem specimens were assessed histologically to examine the efficacy of the models. Results In the tail models, although a substantial frequency of tail necrosis (30.0%) was noted and the increase in circumference was maintained for only limited times postoperatively depending on the particular tail model, the overall success rate was 65.0%. In the mouse hind limb model, the overall success rate was 88.9%, and the increased circumference and limb volume were maintained over the entire study period of 8 weeks. The overall success rate of the mouse hind limb model was significantly higher than that of the mouse tail model(s). Conclusions We have successfully established modified mouse tail and hind limb lymphedema models via only surgical techniques without radiation, which have characteristics of chronic secondary lymphedema. The mouse hind limb model has a higher success rate than the mouse tail model and has advantages of having the healthy contralateral hind limbs as an internal control.