Efficacy and safety of stem cell-based interventions for burn wound healing: A systematic review and meta-analysis of pre-clinical and early clinical evidence

Background: Burn injuries remain a major therapeutic challenge, with conventional treatments often failing to achieve complete functional skin regeneration. Stem cell-based interventions, including mesenchymal stem cells (MSCs) and exosome derivatives, have demonstrated regenerative and immunomodulatory potential, yet their translation to clinical practice remains limited. Objectives: To systematically evaluate the efficacy and safety of stem cell-based therapies for burn wound healing across pre-clinical and clinical studies. Materials and Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, four databases (PubMed, Embase, Scopus, and Cochrane) were searched through April 2025. Eligible studies included randomized controlled trials and controlled pre-clinical studies comparing stem cell-based interventions with standard care or placebo. Risk of bias (RoB) was assessed using RoB 2 and the Systematic Review Centre for Laboratory Animal Experimentation tools, and evidence certainty was rated using GRADE. Results: Four studies met the inclusion criteria: One early-phase clinical trial and two pre-clinical randomized studies (MSC extract and exosome therapy). Pooled analysis of pre-clinical data showed a moderateto- large effect favoring stem cell interventions (standardized mean difference = 1.15; 95% confidence interval 0.54–1.76; I2 = 49.4%). Certainty of evidence was moderate for efficacy and low for safety. Conclusion: Stem cell-based therapies suggest potential benefit in enhancing burn wound healing, yet the evidence remains preliminary and largely pre-clinical. These interventions should be regarded as investigational, pending well-powered multicenter clinical trials with standardized protocols and long-term safety evaluation.