Extracellular Vesicle Associated MicroRNAs in Vitiligo: A Systematic Review of Mechanisms and Translational Potential

Background: Extracellular vesicle (EV)-associated microRNAs may contribute to vitiligo-related melanocyte and immune-cell changes. This review evaluates their mechanistic and translational evidence while distinguishing biological compartments and experimental models. Methods: Searches covered six information sources from database inception up to 30 April 2026. Three authors screened reports and three extracted data, with disagreements referred to designated adjudicators. Bias was appraised using an adapted Cochrane domain-based framework. No registration identifier was reported. Evidence was synthesized by design and EV source; heterogeneity precluded meta-analysis. Results: Seven studies examined keratinocyte EVs, circulating EV-enriched fractions, human umbilical cord mesenchymal stem cell (hUMSC) EVs, or computational datasets. Cellular experiments linked miR-200c and miR-21-5p to melanogenesis and miR-493-3p to keratinocyte dopamine handling in segmental vitiligo. miR-1469 was associated with non-segmental vitiligo activity and natural killer (NK)-cell regulation. A small longitudinal miR-487b-3p study reported an exploratory area under the receiver operating characteristic curve of 0.840 for pretreatment versus post-treatment samples. hUMSC-EV experiments distinguished miR-125b-5p/BAK1-mediated melanocyte protection from miR-132-3p/SIRT1-mediated regulatory T-cell differentiation. Computational associations provided hypothesis-generating evidence. Conclusion: Evidence supports selected experimental mechanisms and exploratory biomarker candidates. Small samples, heterogeneous methods, incomplete retrieval accounting, and lack of established external clinical validation limit inference. EV-based microRNA therapies remain preclinical. Keywords: extracellular vesicles, microRNA, vitiligo, systematic review, biomarker candidates, translational potential