Application and prospect of adipose stem cell transplantation in treating lymphedema

Abstract

BACKGROUND Lymphedema is a chronic, debilitating and incurable disease that affects 0.13%-2% of the global population. Emerging evidence indicates that adipose-derived stem cells (ADSCs) might serve as suitable seed cells for lymphatic tissue engineering and lymphedema therapy. AIM To summarize applications of ADSCs for treating lymphedema in both animal studies and clinical trials. METHODS A systematic search was performed on four databases – PubMed, Clinicaltrials.gov, the evidence-based Cochrane Library, and OVID – using the following search string: (“lymphedema” or “lymphoedema” or “lymphangiogenesis”) and (“adipose-derived stem cells” or “adipose-derived stromal cells” or “adipose-derived regenerative cells”). A manual search was performed by skimming the references of relevant studies. Animal studies and clinical trials using adipose-derived cells for the treatment of any kind of lymphedema were included. RESULTS A total of eight research articles published before November 2019 were included for this analysis. Five articles focused on animal studies and another three focused on clinical trials. ADSC transplantation therapy was demonstrated to be effective against lymphedema in all studies. The animal studies found that coadministration of ADSCs and controlled-release vascular endothelial growth factor-C or platelet-rich plasma could improve the effectiveness of ADSC therapy. Three sequential clinical trials were conducted on breast cancer-related lymphedema patients, and all showed favorable results. CONCLUSION ADSC-based therapy is a promising option for treating lymphedema. Large-scale, multicenter randomized controlled trials are needed to develop more effective and durable therapeutic strategies.

Hormone Therapy: A Potential Risk Factor Affecting Survival and Functional Restoration of Transplanted Lymph Nodes

“…Increasing evidence indicates that there is an intrinsic correlation between adipose tissue and the lymphatic system. According to previous studies ( Takeda et al, 2015 ; Li et al, 2020 ), adipose-derived stem cells (ADSCs) could promote proliferation, migration, and tube formation of LECs in vitro by secreting various lymphangiogenic factors. In addition, it has been demonstrated that ADSCs can increase the number of lymphatic vessels and promote the restoration of lymphatic drainage in vivo ( Hayashida et al, 2017 ; Hu and Pan, 2020 ).…”

Cell therapy as a treatment of secondary lymphedema: a systematic review and meta-analysis

“…We found that cell therapy proved to generate a robust beneficial effect in animal models of secondary lymphedema. Although several in vitro and in vivo studies have reported beneficial effects of cell therapy against secondary lymphedema [ 21 , 49 , 50 ], a formal meta-analysis that assesses the regenerative activity of cell therapy in animal models of secondary lymphedema had not been performed.…”

Visual analysis of global research output of lymphedema based on bibliometrics

“…In clinical trials, the safety of the combination of lymph node metastasis and adenoviral VEGF-C was demonstrated in a small trial of lymphedema associated with breast cancer (62). Danish research groups pioneered clinical trials of adipose-derived regenerative cells for lymphedema, and in 2016, Toyotaserkani et al reported a pilot study using adipose stem cells adjuvant fat transfer for lymphedema, where 4 weeks after treatment, patients' daily arm heaviness, tension symptoms were significantly reduced, the number of compression treatments was decreased, the volume of the affected limb was reduced, and no postoperative complications or adverse events occurred; and they were conducting a phase III clinical trial (63,64). As discussed above, a better understanding of how different genes or molecules affect the normal function of the lymphatic vascular system and the identification of new pro-lymphopoietic factors will help in the diagnosis and eventual treatment of patients with symptomatic or asymptomatic lymphatic disorders and related comorbidities.…”