Contralateral Vascularized Lymph Node Transfer: An Optimized Mouse Model

Abstract

Background Vascularized lymph node transfer (VLNT) is one of the surgical options in the treatment of lymphedema, but its mechanism of action has not yet been firmly clarified. In the VLNT mouse models described so far, the lymph node flap is performed between two different sites in the same lymphedematous paw. In this study, we describe an optimized VLNT mouse model using the contralateral paw as donor site, thus removing the bias of transferring a lymph node already damaged by irradiation and/or surgery required to induce lymphedema. Methods A lymphedema was induced on the left posterior paw in four experimental groups of mice (n = 8). Two weeks later, group 1 was the sham one, group 2 underwent a VLNT from the right inguinal region to the left, in group 3 a vascular endothelial growth factor (VEGF)-C sponge was placed alone in the left inguinal region, and in group 4 a VEGF-C sponge was associated to the VLNT. The 32 mice were followed during 3 months. Outcomes included paws volume, skin quality, inflammation in the lymphedematous tissue, and lymphatic network density and function. Results Group 4 displayed significantly higher (p < 0.05) lymphedema regression compared with the other three groups. Conclusions This optimized mouse model of VLNT shows to be handy and effective. It could be exploited to perform further experimental studies about the influence of VLNT on lymphedema. Moreover, the local association between VLNT and biological compounds in this model allows it to be a good preclinical model to identify new potential drugs in lymphedema.