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

Abstract

Background Lymphedema, the accumulation of interstitial fluid caused by poor lymphatic drainage, is a progressive and permanent disease with no curative treatment. Several studies have evaluated cell-based therapies in secondary lymphedema, but no meta-analysis has been performed to assess their efficacy. Methods We conducted a systematic review and meta-analysis of all available preclinical and clinical studies, with assessment of their quality and risk of bias. Results A total of 20 articles using diverse cell types were selected for analysis, including six clinical trials and 14 pre-clinical studies in three species. The meta-analysis showed a positive effect of cell-based therapies on relevant disease outcomes (quantification of edema, density of lymphatic capillaries, evaluation of the lymphatic flow, and tissue fibrosis). No significant publication bias was observed. Conclusion Cell-based therapies have the potential to improve secondary lymphedema. The underlying mechanisms remain unclear. Due to relevant heterogeneity between studies, further randomized controlled and blinded studies are required to substantiate the use of these novel therapies in clinical practice.

Recellularized lymph node scaffolds with human adipose-derived stem cells enhance lymph node regeneration to improve lymphedema

“…When there is a problem with the lymphatic circulation, fluid accumulates in the interstitial space 17 . Recently, the incidence of lymphedema is increasing due to surgery and radiotherapy related to malignant neoplasms 11 , 16 . Most of the standard treatment for lymphedema is physiotherapy such as lymphatic drainage and compression bandage.…”

“…In addition, cell therapy for treatment of lymphedema is being actively conducted. Stem cells have various effects such as anti-inflammatory, anti-fibrotic, and tissue regeneration promotion, so they can promote lymphatic regeneration and improve interstitial fluid drainage 11 . Cell therapy included stem cells such as d bone marrow-derived mesenchymal stem cells (BM-MSCs), ADSCs, human LECs, and regulatory T cells, and studies including growth factors such as VEGF-C were conducted [12][13][14][15] .…”

Establishment of a Simple, Reproducible, and Long-lasting Hind Limb Animal Model of Lymphedema

“…The therapeutic effects, practicality, and safety of MSC transplantation for lymphedema have been assessed in some animal and clinical studies. 3 , 4 Although the preferable therapeutic effects of MSCs for lymphedema have been elucidated, it is still unclear which cytokines derived from MSCs harbor a specific effect on improvement of this disease. Further detailed studies are needed.…”

“…2 The potentially useful radical therapy of mesenchymal stem cell (MSC) transplantation has been discussed. 3,4 Appropriate and reliable animal models that reproduce the pathophysiology of lymphedema are essential for the development of better treatments and assessment of their usefulness. However, the published models are limited in that the lymphedema is short lived, 5 resolving spontaneously over time with most available surgical models.…”

“… 2 The potentially useful radical therapy of mesenchymal stem cell (MSC) transplantation has been discussed. 3 , 4 …”