Stem Cell-Based Therapies for Scarless Skin Repair

Scar formation after skin injury remains a significant clinical problem, affecting millions of people each year with important aesthetic, functional and economic sequelae. Mammalian fetal skin regenerates in a scarless manner until about 24 weeks gestation, unlike adult wound healing where it results in avascular, disorganized scar formation, thus providing a developmental model for adult repair. This review summarizes recent advances in stem cell-based therapy for scarless skin regeneration, including cutaneous stem cell niches (EpSCs, HFSCs, MSCs, ASCs), key signaling pathways (Wnt/β-catenin, YAP, TGF-β/Smad), and novel strategies such as extracellular vesicles and biomaterial-assisted delivery. Preclinical studies have demonstrated the ability of stem cell transplantation to improve wound healing by accelerating wound closure, increasing vascularization and modulating inflammation. Nevertheless, issues of reproducibility, standardization, and inadequate preclinical model systems limit their use in the clinic. Future integration of genome editing, organoids, bioprinting and multi-omics will fill this gap. Overall, stem cell-based approaches represent a paradigm shift from passive anti-fibrosis to active regeneration, with transformative potential for functional skin restoration.