Abstract
Alopecia areata (AA) is an autoimmune-mediated nonscarring alopecia with limited therapeutic options and frequent relapses. Exosomes, nanosized extracellular vesicles secreted by various cell types, have recently emerged as potential regenerative and immunomodulatory therapies. The aim of the study is to review the clinical and preclinical evidence regarding the efficacy and safety of EV-based therapies for alopecia areata. a systematic search of PubMed, Embase, Web of Science, and Cochrane Library was performed from 2020 to 2 October 2025. Inclusion criteria were original studies (clinical, preclinical, in vivo, in vitro) investigating exosome-derived interventions for AA. Outcomes of interest were hair regrowth, immune modulation, follicular regeneration, and safety. A total of 499 records were retrieved from electronic database searches. After deduplication and application of the inclusion/exclusion criteria, 40 studies met the eligibility criteria for the review. Of these, two were clinical studies (one retrospective cohort, one case report), while the remainder comprised five animal (in vivo) studies, six in vitro studies, and sixteen mixed translational studies (in vitro/in vivo ± clinical). Experimental studies reported hair coverage improvements of 50-99% and, in one instance, 30% regrowth in totalis and 16% in partialis, with nearly complete regrowth in incipient alopecia. Clinical reports noted density increases of 9-31 hairs per cm(2) (e.g., from 121.7 to 146.6 hairs/cm(2), p < 0.001) and improvements in hair count, length, and thickness. Several studies detailed activation of the Wnt/β-catenin pathway along with enhanced dermal papilla and hair follicle stem cell function, as well as anti-inflammatory effects. Reported safety profiles were favorable; when adverse events occurred, they were limited to mild, transient local reactions with no severe systemic issues. EV-based therapy is a novel and biologically plausible approach for AA, but robust randomized controlled trials (RCTs) are lacking. Standardization of small EV sources, doses, and delivery methods is essential before clinical translation.