Comparison of avascular lymph node fragment transplantation techniques to optimize lymphangiogenesis in the minipig model

BACKGROUND: Secondary lymphoedema is a challenging pandemic. This condition may arise after oncologic resection of tumor-draining lymph nodes and/or radiation. Plastic-surgical procedures for lymphoedema comprise transplantation of vascularized lymph node flaps, which are, however, technically challenging and difficult to implement on a global level due to the scarcity of microsurgery facilities in some countries. To improve this situation, comparative research in valid animal models is needed. METHODS: A total of 33 minipigs were subjected to lymphatic resection in the hind limbs. This large animal model was used in a first phase to compare different lymph node fragmentation methods and assess lymphatic regeneration after avascular transplantation. In a second phase, several stimulants were tested for their effect on lymphatic regeneration after fragment transplantation. In a third phase, animals additionally received irradiation of the groin. In this novel animal model, autologous avascular lymph node fragment transplantation was complemented by peripheral injections of vascular endothelial growth factor-C (VEGF-C). Finally, regeneration rates were quantified in relative numbers (percentage) in the irradiated tissue. RESULTS: In the first phase, transversal lymph node fragmentation under preservation of the nodal capsule showed the best percentage of regeneration (62.5%). Peripheral intradermal administration of VEGF-C enhanced lymph node fragment regeneration (70.8%) better than injections of tetanus toxoid (41.6%) or Streptococcus suis (62.5%). Lymph node fragment regeneration also occurred in an irradiated porcine model of lymphadenectomy under VEGF-C administration (66.6%). CONCLUSIONS: The present findings provide a pre-clinical proof-of-concept for a possible simplification strategy for current operative procedures of autologous lymph node transplantation. Level of evidence : Not gradable