{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:00:39Z","timestamp":1792803639304,"version":"4.5.0"},"reference-count":63,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u00b1 clinical). Experimental studies reported hair coverage improvements of 50\u201399% 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\u201331 hairs per cm2 (e.g., from 121.7 to 146.6 hairs\/cm2, p &lt; 0.001) and improvements in hair count, length, and thickness. Several studies detailed activation of the Wnt\/\u03b2-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.<\/jats:p>","DOI":"10.3390\/ijms27010021","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:59:57Z","timestamp":1766149197000},"page":"21","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exosome-Based Therapies for Alopecia Areata: A Systematic Review of Clinical and Experimental Evidence"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0145-7269","authenticated-orcid":false,"given":"Andra Irina","family":"Bulgaru-Iliescu","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Department of Plastic Surgery and Reconstructive Microsurgery, Sf. Spiridon Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2571-1496","authenticated-orcid":false,"given":"Dan Cristian","family":"Moraru","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Department of Plastic Surgery and Reconstructive Microsurgery, Sf. Spiridon Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2154-9236","authenticated-orcid":false,"given":"Alexandru-Hristo","family":"Amarandei","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Department of Plastic Surgery and Reconstructive Microsurgery, Sf. Spiridon Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9192-7607","authenticated-orcid":false,"given":"Stefana","family":"Avadanei-Luca","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Department of Plastic Surgery and Reconstructive Microsurgery, Sf. Spiridon Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8538-7811","authenticated-orcid":false,"given":"Mihai-Codrin","family":"Constantinescu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Department of Plastic Surgery and Reconstructive Microsurgery, Sf. Spiridon Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2936-0753","authenticated-orcid":false,"given":"Alexandra Cristina","family":"Rusu","sequence":"additional","affiliation":[{"name":"George Emil Palade University of Medicine, Pharmacy, Science and Technology Targu Mures, 540139 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-7192","authenticated-orcid":false,"given":"Mihaela","family":"Pertea","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Department of Plastic Surgery and Reconstructive Microsurgery, Sf. Spiridon Emergency County Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1016\/j.jisp.2020.04.002","article-title":"The Evolving Pathogenesis of Alopecia Areata: Major Open Questions","volume":"20","author":"Paus","year":"2020","journal-title":"J. Investig. Dermatol. Symp. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1056\/NEJMra1103442","article-title":"Alopecia areata","volume":"366","author":"Gilhar","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"17011","DOI":"10.1038\/nrdp.2017.11","article-title":"Alopecia areata","volume":"3","author":"Pratt","year":"2017","journal-title":"Nat. Rev. Dis. 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