Therapeutic Potential of Mesenchymal Stem Cells for Postmastectomy Lymphedema: A Literature Review

Abstract

Upper limb lymphedema is one of the most common complications after breast cancer surgery and radiotherapy. Despite various physical therapy and surgical options available, the impaired lymph fluid drainage may be progressive due to lymphatic vascular insufficiency making treatment more difficulty. Stem cell therapy provides a promising alternative in the treatment of various chronic diseases. The wide applicability of cell therapy has been reviewed throughout literature. This review provides an overview of recent progress in the therapeutic effect of adult stem cells for primary and secondary lymphedema after breast surgery in preclinical studies and clinical cases. We start with a brief introduction about the pathophysiological mechanisms of postmastectomy lymphedema. Regarding existing treatments, we systematically summarize the benefits and limitations of recent progress. Because of their multidirectional differentiation potential and growth factor secretion, stem cell therapy shows promising results in the management of light to severe lymphedema. Increasing evidences have demonstrated a noticeable reduction in postmastectomy lymphedema and increased lymph‐angiogenesis after specific stem cell therapy. Current data suggests that stem cell therapy in lymphedema treatment provides reversal of pathological reorganization associated with lymphedema progression. Finally, we propose potential strategies for overcoming the challenges in the development of multipotent progenitor cells for the treatment and prevention of lymphedema in clinical practice.

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.…”

“…In the last decade, cell therapy with differentiated or progenitor cells has emerged as a new research target in the therapy of secondary lymphedema [ 21 , 22 ]. Although the cellular pathways through which stem cell therapy could help lymphedema patients are unclear, in vitro studies indicate that stem cells may differentiate into lymphatic endothelial-like cells under in vitro culture conditions and can improve interstitial fluid drainage when injected in vivo [ 13 ].…”

Homeostatic maintenance of the lymphatic vasculature

“…Recent studies assessing the potential of adipose, mesenchymal, and induced pluripotent stem cells for the treatment of lymphedema have shown promising preclinical and clinical outcomes. The positive effects were mediated by the antiinflammatory, antifibrotic, and antioxidative effects of the stem cells, as well as, most importantly, the regeneration of lymphatic conduits [167]. Secondary lymphedema develops mostly in a delayed fashion, often years after the injury.…”

Robot-Assisted Minimally Invasive Breast Surgery: Recent Evidence with Comparative Clinical Outcomes

“…At present, surgery is one of the main approaches for breast cancer treatment [ 5 , 6 , 7 , 8 ]. However, the complications of conventional surgery include lymphedema, fat necrosis, wound infection, range-of-motion restriction, and arm paraesthesia [ 7 , 9 , 10 , 11 , 12 , 13 , 14 ].…”

“…At present, surgery is one of the main approaches for breast cancer treatment [ 5 , 6 , 7 , 8 ]. However, the complications of conventional surgery include lymphedema, fat necrosis, wound infection, range-of-motion restriction, and arm paraesthesia [ 7 , 9 , 10 , 11 , 12 , 13 , 14 ]. Robot-assisted systems for oncologic surgery are approved by the US Food and Drug Administration (FDA) for specific abdominal surgical interventions.…”