Mesenchymal stem cell therapy for breast cancer-related secondary lymphedema (Review)

Abstract

Secondary lymphedema, affecting ~15-30% of patients who survive breast cancer, is a common consequence following treatment. At present, there is no gold standard for the treatment of breast cancer-related lymphedema (BCRL). Conventional methods such as physiotherapy and surgery demonstrate a limited effectiveness in mitigating lymphatic swelling or discomfort and fail to provide substantial physiological improvement or a definitive cure for lymphedema. However, stem cell therapy has garnered notable attention due to its regenerative potential and its capacity to modulate inflammatory processes. Mesenchymal stem cell (MSC) therapies exhibit promise in ameliorating BCRL by addressing edema, promoting lymphangiogenesis and mitigating fibrosis. It is shown that MSC therapy promotes the regeneration of autologous lymphatic networks and improves vascular conditions in rodent tail and hindlimb lymphedema models, which offers relief from lymphedema symptoms including limb volume asymmetry and impaired lymphatic drainage. However, currently, due to a lack of a universally recognized or standardized treatment regimen for BCRL, there is a need for additional clinical studies featuring larger sample sizes and extended follow-up periods to further investigate this prospective therapeutic modality. The present review aims to provide guidance for further research and therapeutic interventions following the results observed in both preclinical and clinical settings. The present study investigated the pathogenesis of secondary lymphedema, previous advancements in stem cell therapy for this condition and an analysis of persisting challenges.

Keywords: BCRL; MSCs; lymphangiography; regulatory T cells.

Figure 1

Formation of lymphedema after lymphatic injury. (A) Lymph flow is facilitated by the intrinsic pump force of the lymphatic vessels, along with the extrinsic pump force generated by skeletal muscles. Following lymphatic damage, such as that caused by surgical resection (for example, lymph node dissection) or radiation therapy in cancer treatments, M2 macrophages and dendritic cells become activated. (B) Activated dendritic and Th cells infiltrate the damaged area and secrete cytokines such as IL-2 and TNF-α. VEGF-C, vascular endothelial growth factor C; CCL, CC chemokine ligand; Th, T helper; CCR, C-C chemokine receptor; CLA, cutaneous lymphocyte-associated antigen.

Figure 2

Stem cell transplantation improves lymphedema. Stem cell transplantation can improve the symptoms of lymphedema including promoting Th cell amplification, angiogenesis and lymphangiogenesis, reducing limb circumference and skin fibrosis, relieving pain, and secreting regenerative cytokines such as vascular endothelial growth factor C and hepatocyte growth factor. Th, T helper.