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

Stem Cell Res Ther. 2021 Nov 20;12(1):578. doi: 10.1186/s13287-021-02632-y.


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.

Keywords: Lymphatic vasculature; Lymphedema; Meta-analysis; Regeneration; Regenerative medicine; Stem cells; Systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Cell- and Tissue-Based Therapy / adverse effects
  • Humans
  • Lymphedema* / etiology
  • Lymphedema* / therapy