Stem Cells-Based Strategies for Skin Regeneration and Repair: Current Approaches, Pre-Clinical, and Clinical Evidence

Purpose of Review Skin regeneration and repair remain major challenges in clinical practice, particularly in the management of chronic wounds, burns, scars, photoaging, and other dermatological conditions. Stem cell-based therapies have emerged as regenerative strategies owing to their ability to self-renew, differentiate into multiple cell lineages, modulate immune responses, and promote tissue repair through paracrine signalling. This review aims to provide a comprehensive overview of current stem cell-based strategies for skin regeneration and repair by summarizing the biological characteristics, mechanisms of action, and therapeutic applications of different stem cell types, along with evidence from preclinical and clinical studies. Recent Findings Recent advances have demonstrated the regenerative potential of mesenchymal stem cells, adipose-derived stem cells, epidermal stem cells, hair follicle stem cells, induced pluripotent stem cells, stem cell-derived extracellular vesicles, and stem cell-conditioned media. Preclinical evidence indicates enhanced angiogenesis, extracellular matrix remodelling, collagen deposition, immunomodulation, and re-epithelialization, resulting in accelerated wound healing and skin regeneration. Early clinical studies have reported encouraging outcomes in the management of diabetic ulcers, burns, alopecia, photoaging, epidermolysis bullosa, and other chronic skin conditions. Moreover, advances in biomaterials, hydrogels, three-dimensional bioprinting, and tissue engineering have enhanced the therapeutic potential and translational feasibility of stem cell-based regenerative therapies. Summary Current evidence suggests that stem cell-based therapies represent a promising strategy for skin tissue regeneration and repair, owing to their regenerative, anti-inflammatory, pro-angiogenic, and immunomodulatory effects. Despite success in preclinical and early clinical studies, several obstacles, including difficulties in standardising stem cell sources, manufacturing scalability, long-term safety, ethical considerations, and regulatory approval, continue to limit widespread clinical application. Future research should focus on conducting well-designed multicentre clinical trials, developing standardized therapeutic protocols, and integrating innovative approaches in biomaterials and tissue engineering. Graphical Abstract