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Table 1. Study characteristics of included animal trials

Study Animal
Author Year Specific aim LO model Outcome Shortcomings
design model
[9]
Pabst et al. 1988 RCAT Minipig Proof of concept of NVLNT None Transplanted lymph nodes demonstrated regrowth at Preliminary, proof of
6 months concept. Not validated in a
lymphoedema model
[5]
Fu et al. 1998 RCAT New Demonstrating NVLNT in mitigating the onset Surgical ligation of Ear volumes in transplanted rabbits approached those Intervention was performed
Zealand lymphoedema in response to surgical auricular lymph vessels of the negative control at 5 months prior to the clinical
white lymphatic disruption Indirect lymphography demonstrated no dermal establishment of
rabbit backflow in transplanted rabbits lymphoedema
[13]
Hadamitzky et al. 2009 RCAT Lewis rats Determining the effect of PRP to augment Surgical ligation of inguinal The introduction of subdermal PRP enhanced rate of As above
lymphangiogenesis lymph vessels lymphangiogenesis even when compared to immune
induction with sheep erythrocytes
[6]
Tobbia et al. 2009 RCAT Dorset Comparing VLNT to NVLNT Surgical ligation of VLNT is more consistent and provides superior As Above
sheep popliteal lymph vessels lymphatic drainage as compared to NVLNT as
quantified by limb volume measures and
lymphangiography
[15]
Blum et al. 2010 RCAT Minipig The effect of various lymph node Surgical ligation of inguinal The optimal fragmentation pattern was when the As above
fragmentation techniques on lymph nodes lymph node was divided into two pieces with the
lymphangiogenesis capsule maintained (Butterfly)
[11]
Lähteenvuo et al. 2011 RCAT Pig Comparing VEGF-C and VEGF-D gene therapy Surgical ligation of inguinal VEGF-C treated subjects demonstrated both As Above
in promoting lymphangiogenesis lymph nodes increased histological lymphangiogenesis as well as
increased functional lymphatic drainage on XR-
Lymphangiography
[19]
Sommer et al. 2012 RCAT Lewis rat Evaluating the effect of VEGF-C gene therapy Surgical ligation of axillary VEGF-C groups demonstrated more robust As Above
on lymphangiogenesis lymph nodes histological lymphangiogenesis as well as a greater
ICG measured lymphosome
[14]
Joseph et al. 2014 RCAT Mouse Comparing the induction of sterile Surgical ligation of inguinal Histological assessment demonstrated that sterile As above
inflammation pre and post lymph node lymph nodes inflammation induced post transplantation resulted in
grafting in lymphangiogenesis the most extensive lymphangiogenesis
[16] [11]
Tervala et al. 2015 RCAT Mouse Similar to Lähteenvuo et al.
[17]
Shioya et al. 2016 RCAT Mouse Demonstrating the efficacy of standard Surgical ligation of ICG lymphangiography and measuring rat paw As above
NVLNT as measured by ICG popliteal lymph nodes volumes demonstrated lymphangiogenesis
lymphangiography
[24]
Hadamitzky et al. 2018 RCAT Minipig Evaluating the effect of cryopreservation of No true lymphoedema Cryopreservation did not hinder the ability of No lymphoedema model
lymph nodes on the lymphangiogenic capacity model as only superficial transplanted lymph nodes to reintegrate
of transplanted lymph nodes lymph nodes were
harvested
[18]
Maeda et al. 2018 RCAT Mouse Evaluating whether microsurgical attachment Surgical ligation of The first documented attempt at restoring anatomical Intervention was performed
of a transplanted lymph node to a recipient popliteal lymph nodes organisation of lymphatics by non-vascularised prior to the clinical
lymphatic vessel would encourage means demonstrated good histological establishment of
lymphangiogenesis lymphangiogenesis lymphoedema
[12]
Hadamitzky et al. 2022 RCAT Minipig Combining existing adjuvants of VEGF-C and Surgical ligation of inguinal Combined VEGF-C and “Butterfly” fragmentation As above