Stem cell-derived secretome: a novel strategy for wound healing.

Chronic non-healing wounds, including diabetic ulcers, venous leg ulcers, and pressure ulcers, represent a significant clinical burden worldwide, associated with major economic costs and impaired quality of life. Although stem cell-based therapies have shown regenerative potential, recent accumulating evidence indicates that their therapeutic effects are primarily mediated by paracrine signaling rather than direct cell engraftment. Stem cell-derived secretome, which consists of soluble bioactive factors and extracellular vesicles, has gained attention as a promising cell-free strategy for wound healing. The secretome modulates inflammation, promotes angiogenesis, supports extracellular matrix remodeling, stabilizes redox homeostasis, and enhances cell survival, proliferation, and migration, thereby creating a pro-regenerative wound microenvironment. Secretome composition is very dynamic and influenced by the stem cell source, donor characteristics, and cell culture conditions, which impacts therapeutic efficacy. Compared with live cell therapies, secretome-based approaches offer improved safety, scalability, and storage potential while avoiding risks associated with cell transplantation. This review provides an overview of the biological processes involved in wound healing, discusses the main stem cell sources used in wound healing, and summarizes current knowledge on stem cell-derived secretome and its mechanisms of action. In addition, emerging delivery strategies, therapeutic advantages, and current challenges associated with secretome-based therapies are discussed, emphasizing their potential in wound regeneration.