Reply: Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic System and Lymphangiogenesis

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The authors very much appreciate the comments and criticisms by Chenglong Wang, Jie Luan, and Minqiang Xin. The authors respectfully reply to their opinions and hope this would make our article “Adipose-Derived Stem Cells and Vascularized Lymph Node Transfers Successfully Treat Mouse Hindlimb Secondary Lymphedema by Early Reconnection of the Lymphatic System and Lymphangiogenesis” in Plastic and Reconstructive Surgery more understandable.
As this model is so consistent, it may be reproducible by many of the researchers in this field, and the secondary lymphedema produced by our method indeed represents clinical secondary lymphedema, and the authors believe applying the word “treat” to the model is most suitable. There would be multiple causes of clinical secondary lymphedema, the most notable of which is surgical damage, especially with lymph node dissection and following adjuvant radiation therapy. The wounds in rodents heal easily compared with humans; thus, to sustain the blockage of skin and fat tissue, this method is mandatory for this model. Among the most important of our research findings is the fact that there are two major lymphatic route in mouse lower limbs: one is the popliteal lymph node route and the other is the subiliac lymph node route. The magnitude of lymphatic flow is much greater in the popliteal route.1 This model demonstrates the restoration of lymphatic vessels and routes and represents the regeneration of the lower limb lymphatic systems.
The metastasis analysis merely demonstrates how quickly both vascularized lymph node transfer and adipose-derived stem cells can restore the lymphatic routes and vessels and lymphangiogenesis. Regardless of how more stringent conditions of secondary lymphedema in rodents are requested, the lymphatic vessels and routes are restored transiently; thus, time-frame setting is very important, and our model is far more sustained compared with previous models.2,3 The carcinogenic effects of adipose-derived stem cells together with malignant cells are still controversial,4 and there are no significant clinical drawbacks in either the literature or in clinical practice.

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