Application of stem cell-derived exosomes in skin wound healing: mechanisms, prospects, and challenges

As the largest organ of the human body, the skin is essential for maintaining systemic homeostasis; however, it remains highly susceptible to injury and wound formation, posing a significant clinical and economic burden. Wound healing is a complex, tightly coordinated process that progresses through overlapping phases of hemostasis, inflammation, proliferation, and tissue remodeling. Exosomes, nanoscale extracellular vesicles (50-150 nm in diameter) secreted by various cell types, have emerged as critical mediators of intercellular communication. Laden with bioactive molecules such as proteins, RNAs, and lipids, exosomes can partially replicate the regenerative functions of their parent cells. Among various types of exosomes, mesenchymal stem cell-derived exosomes (MSC-Exos) have become the most clinically translatable research direction in the field of skin wound repair due to their biological functions similar to those of their parent stem cells, low immunogenicity, and advantages as a cell-free therapy. This review focuses on MSC-Exos and systematically summarizes the roles and underlying mechanisms of adipose-derived stem cell exosomes, bone marrow mesenchymal stem cell exosomes, human umbilical cord mesenchymal stem cell exosomes, antler stem cell exosomes, human urine-derived stem cell exosomes, and induced pluripotent stem cell exosomes in cutaneous wound repair. Additionally, to broaden the diversity of therapeutic sources, plant-derived exosome-like nanovesicles are also discussed as an emerging perspective. Current evidence indicates that these vesicles facilitate wound healing and attenuate scarring by modulating multiple signaling pathways, thereby promoting cell proliferation, migration, angiogenesis, and extracellular matrix remodeling. Nevertheless, challenges in isolation, purification, optimization, standardization, and quality control continue to hinder their broad clinical translation. Despite these obstacles, exosomes represent a promising therapeutic strategy for cutaneous wound healing.