{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:39:09Z","timestamp":1792514349569,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Epidermal permeability barrier defects are associated with several skin diseases, including atopic dermatitis (AD). Using an AD mouse model, we previously demonstrated that topically administered small extracellular vesicles (sEVs) (prepared following the International Society of Extracellular Vesicles recommendations) from human adipose tissue\u2010derived mesenchymal stem cells (ASC) ameliorate skin inflammation and normalize barrier function in parallel with increased ceramide (a key barrier lipid) production. To elucidate\n                    <jats:italic>how<\/jats:italic>\n                    ASC\u2010sEVs alleviate these AD skin abnormalities, we characterized lipids and ceramide metabolic enzymes in ASC\u2010sEVs versus donor ASCs. Our study revealed that free fatty acid, ceramide, and sphingomyelin are enriched in ASC\u2010sEVs versus donor ASCs, while the synthetic enzymes of ceramide (and acidic sphingomyelinase), and sphingosine\u20101\u2010phosphate (sphingosine kinase) are significantly higher in ASC\u2010sEVs versus donor ASCs. Conversely, ceramide (ceramidase), and sphingosine\u20101\u2010phosphate hydrolytic enzymes (sphingosine\u20101\u2010phosphate lyase and sphingosine\u20101\u2010phosphate phosphatase) are lower in ASC\u2010sEVs, suggesting that ceramide and sphingosine\u20101\u2010phosphate levels could elevate in cells that receive ASC\u2010sEVs. ASC\u2010sEV\u2010mediated increases in sphingosine\u20101\u2010phosphate suppress pro\u2010inflammatory cytokine production in AD\u2010model human keratinocytes. Additionally, keratinocyte differentiation, which is required for a competent epidermal permeability barrier, was restored in AD\u2010model human keratinocytes treated with ASC\u2010sEVs. Taken together, cells that endocytose ASC\u2010sEVs can normalize epidermal permeability barrier function as well as alleviate inflammation by stimulating a sphingosine\u20101\u2010phosphate signalling pathway.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70121","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T11:15:24Z","timestamp":1753182924000},"source":"Crossref","is-referenced-by-count":12,"title":["Small EVs From Adipose\u2010Derived MSCs Modulate Epidermal Barrier and Inflammation Via Sphingosine\u20101\u2010Phosphate Signaling Pathway"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8568-8905","authenticated-orcid":false,"given":"Kyong\u2010Oh","family":"Shin","sequence":"first","affiliation":[{"name":"Department of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharmaceutics Hallym University  Chuncheon Republic of Korea"},{"name":"LaSS Lipid Institute (LLI) LaSS Inc.  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9771-0642","authenticated-orcid":false,"given":"Jun Ho","family":"Lee","sequence":"additional","affiliation":[{"name":"ExoCoBio Exosome Institute (EEI) ExoCoBio Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2689-2166","authenticated-orcid":false,"given":"Seungwoo","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharmaceutics Hallym University  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1164-8143","authenticated-orcid":false,"given":"Karin","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharmaceutics Hallym University  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3392-8139","authenticated-orcid":false,"given":"Hahyun","family":"An","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharmaceutics Hallym University  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8802-2364","authenticated-orcid":false,"given":"Joan S.","family":"Wakefield","sequence":"additional","affiliation":[{"name":"Department of Dermatology, School of Medicine, University of California San Francisco, Department of Veterans Affairs Medical Center, San Francisco Northern California Institute for Research and Education  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4508-4212","authenticated-orcid":false,"given":"Dae Hyun","family":"Ha","sequence":"additional","affiliation":[{"name":"ExoCoBio Exosome Institute (EEI) ExoCoBio Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9486-518X","authenticated-orcid":false,"given":"Healim","family":"Lee","sequence":"additional","affiliation":[{"name":"ExoCoBio Exosome Institute (EEI) ExoCoBio Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0037-2774","authenticated-orcid":false,"given":"Kyojin","family":"Lee","sequence":"additional","affiliation":[{"name":"ExoCoBio Exosome Institute (EEI) ExoCoBio Inc.  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5211-5841","authenticated-orcid":false,"given":"Hyunju","family":"Lee","sequence":"additional","affiliation":[{"name":"ExoCoBio Exosome Institute (EEI) ExoCoBio Inc.  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