Mesenchymal stromal cells and their derivatives: A regenerative frontier in burn wound healing

Burn wounds represent complex therapeutic challenges that conventional treatments often fail to address effectively, particularly regarding prolonged healing times, excessive scarring, and recurrent infections. Mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic agent with unique regenerative capabilities specifically suited to burn wound repair through their multifaceted mechanisms, including regenerative, migratory, immunomodulatory, angiogenic, anti-fibrotic, and immunosuppressive potential. The therapeutic efficacy of MSCs is primarily mediated by their secretome, a complex mixture of bioactive factors, growth factors, and extracellular vesicles that orchestrate tissue repair processes. MSC-derived EVs have gained particular attention as cell-free therapeutic alternatives that deliver functional biomolecules while circumventing the limitations associated with direct cell transplantation. This review critically analyzes the specific and irreplaceable roles of MSCs and their derivatives in burn wound healing, focusing on their unique mechanisms of action, therapeutic advantages over conventional approaches, and the molecular pathways that distinguish them as essential therapeutic tools. We examine current evidence demonstrating their superior efficacy in promoting wound closure, reducing scar formation, and accelerating functional tissue regeneration, while identifying key research gaps and challenges that must be addressed for successful clinical translation.