Stem Cell-Based Therapies for Skin Rejuvenation

BACKGROUNDStem cell-based therapies have emerged as promising interventions for skin rejuvenation, yet a comprehensive synthesis of clinical evidence with systematic methodology is lacking. Previous reviews have been narrative in nature, limiting their utility for evidence-based clinical decision-making.

OBJECTIVETo systematically review and critically appraise the efficacy, safety, and mechanisms of stem cell-based therapies for skin rejuvenation, with particular emphasis on mesenchymal stem cells, exosomes, and their derivatives.

METHODSA systematic search of PubMed, Scopus, Web of Science, Cochrane Library, and Embase was conducted from database inception through February 2026. Randomized controlled trials, prospective cohort studies, and case series with ≥ 10 participants evaluating stem cell-based interventions for skin rejuvenation were included. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool for randomized trials and the ROBINS-I tool for non-randomized studies. Primary outcomes included skin elasticity, hydration, wrinkle reduction, and collagen synthesis. Secondary outcomes included safety parameters and durability of effect. Due to heterogeneity in study designs, interventions, and outcome measures, a narrative synthesis was conducted without meta-analysis.

RESULTSA total of 9 primary studies met the inclusion criteria, of which 6 utilized human-derived stem cells or their derivatives (5 randomized controlled trials and 1 prospective cohort study) and 3 utilized non-human cell sources (avian MSCs, plant-derived exosomes, and red deer umbilical cord MSCs). Findings from human-derived studies, representing 703 participants, demonstrate consistent improvements in skin elasticity (ranging from 26% to 34% across individual studies) and collagen synthesis (ranging from 35% to 45%). Umbilical cord-derived MSCs showed anti-inflammatory effects with reductions in inflammatory cytokines ranging from 38.9% to 50.5%. Exosome-based therapies achieved comparable efficacy to cell-based approaches, with reported reductions in facial wrinkles ranging from 16.8% to 25.4% across four human studies (n = 148 participants). Long-term follow-up data, available from a prospective cohort study, demonstrated sustained improvement in 78.8% of patients at 3 years and 52.9% at 5 years; however, these findings require confirmation in additional studies with longer follow-up. The three non-human studies are presented separately as exploratory findings with limited generalizability.

CONCLUSIONThis systematic review synthesizes the available evidence, which is of low to moderate certainty, suggesting that stem cell-based therapies, particularly adipose-derived and umbilical cord-derived mesenchymal stem cells and their exosomes, may represent effective and safe interventions for skin rejuvenation. Findings from individual studies indicate adipose-derived MSCs are associated with improvements in elasticity and collagen synthesis, while umbilical cord-derived cells may offer enhanced anti-inflammatory effects based on a single comparative study. The emergence of exosome-based therapies is promising and may address some safety concerns. However, the evidence base is limited by a small number of studies, significant methodological heterogeneity, a high risk of bias in several included trials, and the inclusion of studies using non-human cell sources with limited generalizability. These limitations mean that effect estimates are uncertain and likely to change with the publication of higher-quality research.

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