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“Butterfly” fragmentation in order to assess lymph nodes increased SPECT-CT and histologically measured
lymphangiogenesis lymphangiogenesis more than either technique alone
[25]
Kim et al. 2023 RCAT Mouse and Examining the dynamics of NVLNT using Surgical Ligation of Immunohistochemistry as well as secondary As above
minipig immunohistochemical testing inguinal lymph nodes investigation methods of lipidol lymphangiography
and MR lymphangiography all favoured NVLNT
compared to a negative control

NVLNT: Non-vascularised lymph node transfer; PRP: platelet-rich plasma; VLNT: vascularised lymph node transfer.

VEGFR-3, and induce endothelial proliferation and tubule formation . This formation has been shown to be omnidirectional and will also attach to existing
[10]
lymphatic channels within the recipient site to bolster the affected lymphatic network [Figure 2] .
[12]

Maturation and remodelling
As a new network of lymphatic channels is formed, the presence of TGF-beta, IFN-gamma, IL-6, and other cytokines released from B Cells, T Cells, and found

in the extracellular matrix of the recipient site regulate and remodel the nascent lymphatic network such that maturation is achieved [Figure 3] [6,13,14] .

Efficacy in animal models
The sum of NVLNT research in experimental animal models has explored its efficacy in inducing lymphangiogenesis and reducing lymphoedema-related
oedema across multiple species. Additionally, the value of adjuvant techniques to optimise the degree of lymphatic regrowth while reducing donor burden,
such as the use of platelet-rich plasma (PRP), exogenous VEGF-C, inducing sterile inflammation of the nodes prior to transplant, and fragmenting lymph

nodes, has been explored.

With regard to the variety of animal models, both small and large animals have been utilised to demonstrate lymphangiogenesis after engraftment. With
regards to smaller animal models, seven studies utilised models such as the Lewis rat, mouse, and New Zealand white rabbit. Six studies utilised larger animal
models such as minipigs, regular pigs, and Dorset sheep. One study utilised both mouse and minipig models. The authors of the papers reported no special
considerations or variables between smaller and larger animal models. Additionally, during analysis, no discernible differences in outcome measures between

small and large animal models were discovered.

[9]
As mentioned earlier, the first experimental proof of NVLNT was in 1988 by Pabst and Rothkötter in a minipig model . This study compared the degree of
histological lymphangiogenesis after NVLNT of both inguinal and mesenteric lymph nodes grafted to either a distal subcutaneous or subfascial site. The
regrowth of the lymphatic architecture in all groups suggested that avascular grafting may be explored in further studies. Furthermore, the study found that
inguinal lymph nodes transplanted in the subdermal plane grew best among the four groups.