Establishment of an Acquired Lymphedema Model in the Mouse Hindlimb: Technical Refinement and Molecular Characteristics
First, to simulate the acquired lymphedema in humans, an ideal lymphedema animal model should be one with a type of chronic and progressive status. Although the authors developed a stable, reproducible postsurgical mouse lymphedema model in their study, the lymphatic fluid stasis sustained for just 1 month, which was different from acquired lymphedema in humans. Thus, this type of lymphedema model can hardly be used for the study of the effectiveness of some surgical therapies such as vascularized lymph node transfer and lymphaticovenous anastomosis, because it would be difficult to determine which factor, spontaneous recovery or the surgical therapy, results in the reduction of the lymphedema.
Second, as we know, the development of animal models to simulate human lymphedema has been challenging because of the remarkable regenerative capacity of the lymphatics and the formation of collateral pathways around the site of obstruction.2 When compared with the control group, the expression of lymphangiogenic factors in lymphedematous tissues of the splinted lymphedema model was obviously increased because this was the normal physiologic reaction of the organism. This is why lymphatic vessels have been damaged in some surgical procedures but lymphedema does not develop in humans. Therefore, if the authors can evaluate the functionality of the newly formed lymphatic vessels, the result will be more convincing.
Third, as to the murine animal model, despite its availability and low cost, the skin structure of mice is different from that of humans. The subcutaneous tissue of mice lacks adipose tissue, which contains the majority of the superficial lymphatic collectors in humans.3 In addition, compared with human extremities, the lymphatic system in the rat extremity did not show the superficial and deep pathways.4 Thus, it is imperative to find other animal models that are much closer to humans for the study of acquired lymphedema in the future.
Moreover, the authors chose another group of mice that underwent sham surgery as the control. From our point of view, it might be more objective to design the study as follows: the inguinal and popliteal lymph nodes are removed and the silicone splint is implanted in one hindlimb; in the other hindlimb, sham surgery is performed. In this way, the individual variation will be reduced to some extent.