Breaking a Vicious Circle: Lymphangiogenesis as a New Therapeutic Target in Wound Healing

The lymphatic system is of fundamental importance in maintaining a fluid balance in the body and tissue homeostasis; it drains protein-rich lymph from the interstitial space and facilitates the release of cells that mediate the immune response. When one tissue is damaged, more cells and tissues work to repair the damaged site. Blood and lymph vessels are particularly important for tissue regeneration and healing. Angiogenesis is the process of the formation of new blood vessels and is induced by angiogenic factors such as VEGF-A; VEGF-C/D-induced lymphangiogenesis and both occur simultaneously during wound healing. After the inflammatory phase, lymphatic vessels suppress inflammation by aiding in the drainage of inflammatory mediators; thus, disorders of the lymphatic system often result in chronic and disabling conditions. It has recently been clarified that delayed wound healing, as in diabetes, can occur as a consequence of impaired lymphangiogenesis. In this review, we have highlighted recent advances in understanding the biology underlying lymphangiogenesis and its key role in wound healing, and the possibility of its pharmacological modulation as a novel therapeutic strategy for the treatment of chronic wounds.