Abstract
Methods for quantitative analysis of long distance lymphatic transport of nanoparticles in live animals are yet to be established. We established a mouse model for analysis of time-dependent transport just beneath the abdominal skin to investigate lymph node-to-lymph node trafficking by in vivo imaging. For this purpose, popliteal lymph nodes (PLNs) as well as efferent and afferent lymphatic vessels, marginal veins, and feeding blood vessels were surgically resected to change the lymphatic flow from footpad injections. Using this model, we observed a novel lymphatic flow from the footpad to the proper axillary lymph node (ALN) via the inguinal lymph node (ILN). This drainage pathway was maintained over 12 weeks. Time-dependent transportation of 1,1′-dioctadecyltetramethyl indotricarbocyanine iodide-labelled liposomes from the footpad to the ILN was successfully quantified by an in vivo imaging system. Moreover, congestion and development of a new collateral lymphatic route was visualised under a lymphedema status. Histological analysis of abdominal skin tissues of this model revealed that PLN resection had no effect on the abdominal lymphatic system between the ILN and ALN. These data indicate that this model might be useful to clarify the mechanisms of lymphedema and study direct transportation of lymph or other substances between lymph nodes.
Highlights
The lymphatic system has essential functions in cancer progression, lymphedema, and chronic inflammation[1,2]
We developed an advanced surgical method for resection of the popliteal lymph nodes (PLNs) to induce inguinal lymph nodes (LNs) (ILN)-directed lymphatic flow for at least 12 weeks
Development of a novel ILN-mediated lymphatic flow pathway from the footpad to the axillary LN (ALN) was confirmed at 1 week after resection of the PLN
Summary
The lymphatic system has essential functions in cancer progression, lymphedema, and chronic inflammation[1,2]. Kwon et al reported[17] that the drainage pattern changes dramatically after PLN resection, and all injected fluorescence dye (ICG) injected to the footpad drains to the ILN This modified lymphatic route is temporary because the route of lymphatic flow from the paw to the ischial LN via the resected PLN region recovers after approximately 20 days. To evaluate the lymphatic flow in lymphedema, a mouse model that retains the ILN-directed lymphatic flow for a longer period is necessary because induction of lymphoedematous conditions generally requires at least 12 weeks[18] Such a mouse model might allow quantitative analysis of lymphatic transport of nanoparticles with high reproducibility
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