{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:52:56Z","timestamp":1764874376314,"version":"3.46.0"},"reference-count":23,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Medicine and Hygiene Program of Zhejiang Province, Youth Innovation Project","award":["No. 2023RC064"],"award-info":[{"award-number":["No. 2023RC064"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Vitiligo, a chronic autoimmune disease linked to excess oxidative stress, can be temporarily improved. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (BMSCs-Exos) have recently emerged as a promising novel therapeutic means for vitiligo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Exosomes were isolated and characterized from BMSCs-conditioned medium. PIG3V cells and those transfected with\n                      <jats:italic>NRF2<\/jats:italic>\n                      siRNA or negative control were cultured under normal conditions or exposure to hydrogen peroxide (H\u2082O\u2082) to induce oxidative stress, with addition of BMSCs-conditioned medium, conditioned medium from BMSCs pretreated with GW4869 (referred to as BMSCs-GW4869), or BMSCs-Exos. Cell viability, apoptosis, and oxidative stress parameters, including cellular glutathione (GSH)\/oxidized glutathione (GSSG) ratio, superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA), were assessed. The expression of Ki67, NRF2, HO1, BAC, and Bcl-2 was measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BMSC-Exos significantly enhanced cell viability and reduced apoptosis and oxidative stress in H\u2082O\u2082-treated PIG3V cells. Simultaneously, BMSCs-Exos reversed H\u2082O\u2082-induced downregulation of Ki67, NRF2, HO1, and Bcl-2, and upregulation of BAX in PIG3V cells. Silencing\n                      <jats:italic>NRF2<\/jats:italic>\n                      by siRNA in PIG3V cells prior to H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      treatment abolished the protective effect of BMSCs-Exos and decreased the HO1 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>BMSCs-Exos protect melanocytes from vitiliog-related oxidative stress by mitigating oxidative damage through induction of NRF2\/HO1 expression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0338323","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:47:36Z","timestamp":1764874056000},"page":"e0338323","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exosomes from bone marrow mesenchymal stem cells protect melanocytes under vitiligo-related conditions through induction of NRF2\/HO1 expression"],"prefix":"10.1371","volume":"20","author":[{"given":"Xuecheng","family":"Sun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gaobo","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9673-0766","authenticated-orcid":true,"given":"Aie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"issue":"6","key":"pone.0338323.ref001","doi-asserted-by":"crossref","DOI":"10.1002\/ski2.460","article-title":"Vitiligo: From mechanisms of disease to treatable pathways","volume":"4","author":"GN Pathak","year":"2024","journal-title":"Skin Health Dis"},{"issue":"6","key":"pone.0338323.ref002","article-title":"Estimating the burden of vitiligo: a systematic review and modelling study","volume":"9","author":"J Akl","year":"2024","journal-title":"Lancet Public Health"},{"key":"pone.0338323.ref003","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-100919-023531","article-title":"Vitiligo: Mechanisms of Pathogenesis and Treatment","volume":"38","author":"ML Frisoli","year":"2020","journal-title":"Annu Rev Immunol"},{"issue":"17","key":"pone.0338323.ref004","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1007\/s00018-019-03125-1","article-title":"Biological functions of mesenchymal stem cells and clinical implications","volume":"76","author":"A Naji","year":"2019","journal-title":"Cell Mol Life Sci"},{"key":"pone.0338323.ref005","doi-asserted-by":"crossref","first-page":"101766","DOI":"10.1016\/j.trim.2022.101766","article-title":"Vitiligo: An immune disease and its emerging mesenchymal stem cell therapy paradigm","volume":"76","author":"M Zhang","year":"2023","journal-title":"Transpl Immunol"},{"issue":"37","key":"pone.0338323.ref006","doi-asserted-by":"crossref","first-page":"4815","DOI":"10.2174\/1381612826666200730221446","article-title":"Stem Cell Therapy Offers a Possible Safe and Promising Alternative Approach for Treating Vitiligo: A Review","volume":"26","author":"D Esquivel","year":"2020","journal-title":"Curr Pharm Des"},{"issue":"1","key":"pone.0338323.ref007","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1007\/s11033-024-09592-5","article-title":"Capsaicin combined with stem cells improved mitochondrial dysfunction in PIG3V cells, an immortalized human vitiligo melanocyte cell line, by inhibiting the HSP70\/TLR4\/mTOR\/FAK signaling axis","volume":"51","author":"Y Wu","year":"2024","journal-title":"Mol Biol Rep"},{"issue":"1","key":"pone.0338323.ref008","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s13287-019-1543-z","article-title":"Mesenchymal stem cells promote human melanocytes proliferation and resistance to apoptosis through PTEN pathway in vitiligo","volume":"11","author":"L Zhu","year":"2020","journal-title":"Stem Cell Res Ther"},{"issue":"1","key":"pone.0338323.ref009","first-page":"84","article-title":"Bio-inspired adhesive porous particles with human MSCs encapsulation for systemic lupus erythematosus treatment","volume":"6","author":"M Nie","year":"2020","journal-title":"Bioact Mater"},{"issue":"8","key":"pone.0338323.ref010","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.jcyt.2015.04.007","article-title":"Early neuroprotective effect with lack of long-term cell replacement effect on experimental stroke after intra-arterial transplantation of adipose-derived mesenchymal stromal cells","volume":"17","author":"S-H Oh","year":"2015","journal-title":"Cytotherapy"},{"issue":"11","key":"pone.0338323.ref011","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1161\/CIRCRESAHA.110.239848","article-title":"Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy","volume":"108","author":"J-O Jeong","year":"2011","journal-title":"Circ Res"},{"issue":"6478","key":"pone.0338323.ref012","doi-asserted-by":"crossref","DOI":"10.1126\/science.aau6977","article-title":"The biology, function, and biomedical applications of exosomes","volume":"367","author":"R Kalluri","year":"2020","journal-title":"Science"},{"issue":"4","key":"pone.0338323.ref013","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"G van Niel","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"9","key":"pone.0338323.ref014","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.3390\/ijms18091852","article-title":"Mesenchymal Stem Cell Secretome: Toward Cell-Free Therapeutic Strategies in Regenerative Medicine","volume":"18","author":"FJ Vizoso","year":"2017","journal-title":"Int J Mol Sci"},{"issue":"3","key":"pone.0338323.ref015","doi-asserted-by":"crossref","first-page":"350","DOI":"10.3390\/ph17030350","article-title":"An Overview of Mesenchymal Stem Cell Heterogeneity and Concentration","volume":"17","author":"E Mali\u010dev","year":"2024","journal-title":"Pharmaceuticals (Basel)"},{"key":"pone.0338323.ref016","doi-asserted-by":"crossref","first-page":"787118","DOI":"10.3389\/fcell.2021.787118","article-title":"Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation","volume":"9","author":"Q Gao","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"pone.0338323.ref017","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s11481-025-10205-6","article-title":"Exploring Anticonvulsant Effects of Pomalidomide by Targeting Oxidative Stress and Nrf2-Ho1 Signaling Pathway in Male Wistar Rats: A New Insight in Seizure Control","volume":"20","author":"E Khorasanian","year":"2025","journal-title":"J Neuroimmune Pharmacol"},{"key":"pone.0338323.ref018","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.neuro.2023.11.010","article-title":"\u03b1-Pyrrolidinononanophenone derivatives induce differentiated SH-SY5Y neuroblastoma cell apoptosis via reduction of antioxidant capacity: Involvement of NO depletion and inactivation of Nrf2\/HO1 signaling pathway","volume":"100","author":"Y Sakai","year":"2024","journal-title":"Neurotoxicology"},{"issue":"20","key":"pone.0338323.ref019","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.3390\/nu15204325","article-title":"Effects of Gestational and Lactational Lead Exposure and High Fat Diet Feeding on Cerebellar Development of Postnatal Rat Offspring","volume":"15","author":"JS Seo","year":"2023","journal-title":"Nutrients"},{"issue":"6378","key":"pone.0338323.ref020","doi-asserted-by":"crossref","DOI":"10.1126\/science.aao6047","article-title":"BAK\/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis","volume":"359","author":"K McArthur","year":"2018","journal-title":"Science"},{"issue":"7850","key":"pone.0338323.ref021","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/s41586-021-03258-z","article-title":"De novo design of modular and tunable protein biosensors","volume":"591","author":"A Quijano-Rubio","year":"2021","journal-title":"Nature"},{"issue":"31","key":"pone.0338323.ref022","doi-asserted-by":"crossref","DOI":"10.4028\/b-wjQRP6","article-title":"3D-hUMSCs Exosomes Ameliorate Vitiligo by Simultaneously Potentiating Treg Cells-Mediated Immunosuppression and Suppressing Oxidative Stress-Induced Melanocyte Damage","volume":"11","author":"Q Wang","year":"2024","journal-title":"Adv Sci (Weinh)"},{"issue":"1","key":"pone.0338323.ref023","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3892\/mmr.2021.12522","article-title":"Repigmentation by combined narrow\u2011band ultraviolet B\/adipose\u2011derived stem cell transplantation in the mouse model: Role of Nrf2\/HO\u20111\u2011mediated Ca2+ homeostasis","volume":"25","author":"Y Bian","year":"2022","journal-title":"Mol Med Rep"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0338323","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T18:47:41Z","timestamp":1764874061000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0338323"}},"subtitle":[],"editor":[{"given":"Vikash","family":"Chandra","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,4]]},"references-count":23,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0338323","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,4]]}}}