Lymphatic Tissue Engineering: A Further Step for Successful Lymphedema Treatment

Abstract

Background Secondary lymphedema, caused by oncologic surgery, radiation, and chemotherapy, is one of the most relevant, nononcological complications affecting cancer survivors. Severe functional deficits can result in impairing quality of life and a societal burden related to increased treatment costs. Often, conservative treatments are not sufficient to alleviate lymphedema or to prevent stage progression of the disease, as they do not address the underlying etiology that is the disruption of lymphatic pathways. In recent years, lymphatic surgery approaches were revolutionized by advances in microsurgical technique. Currently, lymphedema can effectively be treated by procedures such as lymphovenous anastomosis (LVA) and lymph node transfer (LNT). However, not all patients have suitable lymphatic vessels, and lymph node harvesting is associated with risks. In addition, some data have revealed nonresponders to the microsurgical techniques. Methods A literature review was performed to evaluate the value of lymphatic tissue engineering for plastic surgeons and to give an overview of the achievements, challenges, and goals of the field. Results While certain challenges exist, including cell harvesting, nutrient supply, biocompatibility, and hydrostatic properties, it is possible and desirable to engineer lymph nodes and lymphatic vessels. The path toward clinical translation is considered more complex for LNTs secondary to the complex microarchitecture and pending final mechanistic clarification, while LVA is more straight forward. Conclusion Lymphatic tissue engineering has the potential to be the next step for microsurgical treatment of secondary lymphedema. Current and future researches are necessary to optimize this clinical paradigm shift for improved surgical treatment of lymphedema.

Adipose tissue-derived microvascular fragments promote lymphangiogenesis in a murine lymphedema model

“… 1 , 32 , 33 Moreover, lymphangiogenesis may also be critical for the integration of bioengineered scaffolds. 7 , 16 , 34 A clinically relevant target for lymphatic tissue engineering is the restoration of lymphatic function in lymphedema. Currently, there is no cure for this lifelong and debilitating disease and successful engineering of the lymphatic system might pave the way for novel therapeutic approaches.…”

“…In the last decades, several treatment strategies have been suggested to tackle lymphedema, including reconstructive microsurgery, 3 , 4 pharmacological approaches 5 , 6 or lymphatic tissue engineering. 7 Specifically for the latter, experimental evidence is scarce because mimicking lymphedema in animal models is challenging. 8 …”

Update in the management of lipedema

“…In lipo-lymphedema (combination of lipedema with manifest lymphatic insufficiency) when the advanced stage of lymphedema remains refractory to conventional conservative therapy lymphatic microsurgery could really be a treatment option. 93 Nevertheless, nomenclature seems to be incoherent in the determination of lipedema. The most advanced form of lymphedema with giant adipose tissue enlargement due to severe lymphatic congestion is occasionally labeled as secondary lipedema.…”

Characterization of Immune Cell Infiltration and Collagen Type III Disorganization in Human Secondary Lymphedema: A Case-control Study

“…18,19 At the clinical level, the treatment of cell-mediated inflammation in SL seems promising. 20 The continuous use of nonsteroidal antiinflammatory drugs has been found to reverse experimental SL in a mouse tail model 21 and reduce skin thickness and histopathologic abnormalities in both an open-label and placebocontrolled clinical trial. 22 SL preclinical models provide important mechanistic insights, such as in preventing SL development through neutralizing CD4 + cells with antibodies or applying topical tacrolimus immunosuppression following SL induction.…”