{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:49:48Z","timestamp":1792036188280,"version":"4.4.0"},"reference-count":91,"publisher":"Wiley","issue":"57","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u2010RS\u20102025\u201019612993"],"award-info":[{"award-number":["NRF\u2010RS\u20102025\u201019612993"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102022R1A2C1008368"],"award-info":[{"award-number":["NRF\u20102022R1A2C1008368"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u20102021R1C1C2005005"],"award-info":[{"award-number":["NRF\u20102021R1C1C2005005"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF\u2010RS\u20102019\u2010NR040056"],"award-info":[{"award-number":["NRF\u2010RS\u20102019\u2010NR040056"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ischemic stroke induces oxidative stress, neuroinflammation, neuronal death, and synaptic dysfunction, leading to persistent motor and cognitive deficits. The human dental pulp stem cell (hDPSC) secretome is a promising cell\u2010free therapeutic candidate containing neurotrophic, antioxidant, and immunomodulatory factors. Here, we investigated its therapeutic effects in a photothrombotic mouse model of ischemic stroke and CoCl\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced hypoxic BV2 microglial cells. Proteomic profiling identified antioxidant\u2010associated proteins, including SOD2, GSR, and GSTP1, and microglial phenotype\u2010related candidates, including GRN, CSF1, and LRP1. hDPSC secretome treatment reduced stroke\u2010induced infarct volume and attenuated stroke\u2010increased neuronal apoptosis, neuronal ROS accumulation, and NF\u2010\u03baB\u2010associated inflammatory signaling in the cortex and hippocampus. It also shifted microglial marker expression toward an M2\u2010associated profile and improved stroke\u2010impaired hippocampal neurogenesis, vascular remodeling, and synaptic organization. Proteomic analyses further identified coordinated changes in pathways related to oxidative phosphorylation, inflammatory responses, calcium signaling, SNARE\u2010associated vesicular transport, and ROBO\u2013Rho\u2010associated cytoskeletal remodeling. These molecular and cellular changes were associated with improved motor coordination, spatial learning and memory, contextual memory, and anxiety\u2010like behavior. These findings support the hDPSC secretome as a cell\u2010free therapeutic candidate for post\u2010stroke functional recovery linked to redox, inflammatory, neurovascular, and synaptic remodeling.\n                  <\/jats:p>","DOI":"10.1002\/advs.76717","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:19:48Z","timestamp":1784805588000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Human Dental Pulp Stem Cell Secretome Restores Ischemic Stroke\u2013Impaired Motor and Cognitive Functions by Reprogramming Redox and Inflammatory Signaling"],"prefix":"10.1002","volume":"13","author":[{"given":"Kyung\u2010Joo","family":"Seong","sequence":"first","affiliation":[{"name":"Dental Science Research Institute Stem Cell Secretome Research Center Hard\u2010tissue Biointerface Research Center Department of Oral Physiology School of Dentistry Chonnam National University  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sehoon","family":"Park","sequence":"additional","affiliation":[{"name":"GIST InnoCORE AI\u2010Nano Convergence Institute for Early Detection of Neurodegenerative Diseases Gwangju Institute of Science and Technology  Gwangju Republic of Korea"},{"name":"Department of Life Sciences Gwangju Institute of Science and Technology  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun\u2010Woong","family":"Bae","sequence":"additional","affiliation":[{"name":"Dental Science Research Institute Stem Cell Secretome Research Center Hard\u2010tissue Biointerface Research Center Department of Oral Physiology School of Dentistry Chonnam National University  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daseul","family":"Kim","sequence":"additional","affiliation":[{"name":"GIST InnoCORE AI\u2010Nano Convergence Institute for Early Detection of Neurodegenerative Diseases Gwangju Institute of Science and Technology  Gwangju Republic of Korea"},{"name":"Department of Life Sciences Gwangju Institute of Science and Technology  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Technology Chonnam National University  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won\u2010Seok","family":"Choi","sequence":"additional","affiliation":[{"name":"School of Biological Sciences and Technology Chonnam National University  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zee\u2010Yong","family":"Park","sequence":"additional","affiliation":[{"name":"GIST InnoCORE AI\u2010Nano Convergence Institute for Early Detection of Neurodegenerative Diseases Gwangju Institute of Science and Technology  Gwangju Republic of Korea"},{"name":"Department of Life Sciences Gwangju Institute of Science and Technology  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Yeon","family":"Jung","sequence":"additional","affiliation":[{"name":"Dental Science Research Institute Stem Cell Secretome Research Center Hard\u2010tissue Biointerface Research Center Department of Oral Physiology School of Dentistry Chonnam National University  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6549-744X","authenticated-orcid":false,"given":"Won\u2010Jae","family":"Kim","sequence":"additional","affiliation":[{"name":"Dental Science Research Institute Stem Cell Secretome Research Center Hard\u2010tissue Biointerface Research Center Department of Oral Physiology School of Dentistry Chonnam National University  Gwangju Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000430"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11065-024-09635-5"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1613464"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S461795"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4721"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep00896"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11122377"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01064-1"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.207"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.162"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2735"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20845"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-58688-4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI120412"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aav0618"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/14653240600855905"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-021-00140-6"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/iej.13460"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0979"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.115132"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202415508"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00211"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2023.06.013"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04407-1"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118676"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03264-0"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-00931-2"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02312-w"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.266043"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2025.06.021"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1533"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13557"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.144"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.123490"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00624-2"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12524"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18776802"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.531632"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.09.002"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401963"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202349"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2014.10.016"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1047550"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.12.008"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10966"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-08-02746.1997"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24501"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2020.0701"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.815347"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1440592"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03370-1"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02199"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0772-7"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13139"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-023-02779-w"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-025-00825-0"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-11-146"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.06.082"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2018.22.2.145"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01486-5"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0036-2"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.102315"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00560-10"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13886"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1088417"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2234031100"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910658107"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-025-05473-5"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4323-06.2006"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.111.642710"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114671"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105469"},{"key":"e_1_2_10_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14744"},{"key":"e_1_2_10_75_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.132829"},{"key":"e_1_2_10_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2013.00062"},{"key":"e_1_2_10_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2156"},{"key":"e_1_2_10_78_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067020"},{"key":"e_1_2_10_79_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk0540"},{"key":"e_1_2_10_80_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.1c00259"},{"key":"e_1_2_10_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2024.100723"},{"key":"e_1_2_10_82_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578-022-00786-7"},{"key":"e_1_2_10_83_1","doi-asserted-by":"publisher","DOI":"10.11620\/IJOB.2024.49.4.118"},{"key":"e_1_2_10_84_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci9070165"},{"key":"e_1_2_10_85_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2011.0385"},{"key":"e_1_2_10_86_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.30879"},{"key":"e_1_2_10_87_1","doi-asserted-by":"publisher","DOI":"10.1177\/1545968320926164"},{"key":"e_1_2_10_88_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1040"},{"key":"e_1_2_10_89_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1038"},{"key":"e_1_2_10_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_10_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac194"},{"key":"e_1_2_10_92_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76717","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.76717","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.76717","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:25:12Z","timestamp":1792034712000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.76717"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":91,"journal-issue":{"issue":"57","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/advs.76717"],"URL":"https:\/\/doi.org\/10.1002\/advs.76717","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"assertion":[{"value":"2026-05-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e76717"}}