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These acellular components offer regenerative and immunomodulatory benefits with fewer safety and logistical constraints than cell\u2010based therapies. This study aims to review the composition, mechanisms of action, and dermatologic applications of MSC\u2010derived secretomes and exosomes, including engineered and primed variants, and to discuss translational barriers and safety considerations. A structured literature search was conducted using PubMed and Embase. Studies on molecular content, preclinical and clinical data, engineered EVs, oncologic safety, and regulatory aspects of MSC\u2010derived products in dermatology were included. The MSC secretome includes cytokines, chemokines, growth factors, lipids, and regulatory RNAs that modulate inflammation, promote repair, and support skin homeostasis. Exosomes\u2014particularly those from primed or engineered MSCs\u2014play a key role via targeted microRNA delivery. Preclinical data support efficacy in atopic dermatitis, psoriasis, alopecia areata, vitiligo, chronic ulcers, and photoaging. Pilot clinical trials show promising safety and feasibility for topical or intradermal use. However, product heterogeneity, unclear dosing, long\u2010term oncologic safety, and regulatory challenges persist. MSC\u2010derived secretome and exosomes\u2014especially those from primed or engineered MSCs\u2014offer a promising acellular platform for dermatologic therapy. Clinical translation requires standardization, mechanistic validation, and rigorous safety evaluation through well\u2010designed trials.<\/jats:p>","DOI":"10.1111\/ijd.17982","type":"journal-article","created":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T05:44:54Z","timestamp":1754113494000},"page":"257-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["MSC\u2010Derived Secretome and Exosomes in Dermatology: Mechanisms, Therapeutic Opportunities, and Scientific Challenges\u2014A Narrative Review"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2935-1969","authenticated-orcid":false,"given":"Marcela","family":"da Costa Pereira Cestari","sequence":"first","affiliation":[{"name":"Instituto de Ensino e Pesquisa Hospital S\u00edrio\u2010Liban\u00eas  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinaldo","family":"Falavigna Tovo","sequence":"additional","affiliation":[{"name":"Pontif\u00edcia Universidade Cat\u00f3lica de S\u00e3o Paulo (PUC\u2010SP), Campus Sorocaba  Sorocaba S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Franco Bueno","sequence":"additional","affiliation":[{"name":"Instituto de Ensino e Pesquisa Hospital S\u00edrio\u2010Liban\u00eas  S\u00e3o Paulo S\u00e3o Paulo Brazil"},{"name":"Faculdade Israelita de Ci\u00eancias da Sa\u00fade Albert Einstein  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"e_1_2_24_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.05.004"},{"key":"e_1_2_24_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-014-0260-8"},{"key":"e_1_2_24_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2011.06.008"},{"key":"e_1_2_24_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152300"},{"key":"e_1_2_24_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03630-y"},{"key":"e_1_2_24_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00146"},{"key":"e_1_2_24_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052684"},{"key":"e_1_2_24_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2023.11.009"},{"key":"e_1_2_24_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21207488"},{"key":"e_1_2_24_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02965"},{"key":"e_1_2_24_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346-8138.15743"},{"key":"e_1_2_24_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25179495"},{"key":"e_1_2_24_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.04.009"},{"key":"e_1_2_24_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-100919-023531"},{"key":"e_1_2_24_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11050700"},{"key":"e_1_2_24_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8080886"},{"key":"e_1_2_24_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8834590"},{"key":"e_1_2_24_19_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2004-0359"},{"key":"e_1_2_24_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxae011"},{"key":"e_1_2_24_21_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S331044"},{"key":"e_1_2_24_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00932-0"},{"key":"e_1_2_24_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14119"},{"key":"e_1_2_24_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-022-00863-6"},{"key":"e_1_2_24_25_1","doi-asserted-by":"publisher","DOI":"10.2165\/11596960-000000000-00000"},{"key":"e_1_2_24_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00266-025-04712-3"},{"key":"e_1_2_24_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13329"},{"key":"e_1_2_24_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100090504"},{"key":"e_1_2_24_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240600855905"},{"key":"e_1_2_24_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240500319234"},{"key":"e_1_2_24_31_1","first-page":"855","volume-title":"Stem Cells","author":"Andrzejewska A.","year":"2019"},{"key":"e_1_2_24_32_1","first-page":"393","article-title":"The Development of Fibroblast Colonies in Monolayer Cultures of Guinea\u2010Pig Bone Marrow and Spleen Cells","volume":"3","author":"Friedenstein A. 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