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Page 4 of 13                                                                             Rajaram et al. Plast Aesthet Res. 2025;12:6  https://dx.doi.org/10.20517/2347-9264.2024.147


                              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
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