{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T11:34:04Z","timestamp":1793878444516,"version":"4.7.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030003"],"award-info":[{"award-number":["82030003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82270070"],"award-info":[{"award-number":["82270070"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2019-I2M-5-066"],"award-info":[{"award-number":["2019-I2M-5-066"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2023SHZDZX02"],"award-info":[{"award-number":["2023SHZDZX02"]}]},{"name":"National Key Research and Development Program of China","award":["2023YFC2507100"],"award-info":[{"award-number":["2023YFC2507100"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Stem Cell Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs, leading to significant morbidity and reduced quality of life. Despite ongoing research, the underlying pathogenesis of SSc remains unclear, and treatment options are limited. Stromal vascular fraction (SVF), a naturally occurring cell population that includes mesenchymal stem cells (MSCs), has emerged as a potential therapeutic agent for various fibrotic diseases. This study aimed to investigate the therapeutic effects and underlying mechanisms of SVF in a bleomycin-induced mouse model of skin fibrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>SVF was isolated from the inguinal adipose tissue of C57BL\/6 mice and administered subcutaneously or intradermally at different disease stages to assess its impact on skin fibrosis. Histological analyses were performed to evaluate dermal thickness and collagen deposition. In vivo imaging and immunofluorescence were used to track the retention of SVF within fibrotic tissue over time, particularly in the subcutaneous layer. Flow cytometry and immunofluorescence were employed to examine cutaneous vascular pathology and the secretion of antifibrotic factors, such as hepatocyte growth factor (HGF) and basic fibroblast growth factor (FGF-2). Finally, we investigated the contribution of major SVF subsets to cutaneous fibrosis and the mechanisms by which these subsets mediate therapeutic effects.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>SVF significantly attenuated skin fibrosis in both early and late stages of disease, as evidenced by reduced dermal thickness and collagen deposition. Notably, SVF showed prolonged retention in fibrotic tissues\u2014especially in the subcutaneous layer\u2014for at least 18 days post-injection, with antifibrotic effects primarily mediated through paracrine mechanisms. In early-stage fibrosis, SVF inhibited endothelial\u2013mesenchymal transition and mitigated skin vascular damage. In late-stage fibrosis, SVF continued to secrete antifibrotic factors, including HGF and FGF-2. Subsequent analyses identified the CD45-negative subset of SVF as a key regulator of skin fibrosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>SVF, particularly its CD45-negative subset, holds considerable promise for the treatment of SSc-associated skin fibrosis. These findings suggest that SVF-based therapies could be effective in managing fibrosis-related diseases and offer valuable insights for future clinical applications.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13287-025-04470-8","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T09:52:45Z","timestamp":1751363565000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The stromal vascular fraction mitigates bleomycin-induced skin fibrosis in mice by modulating vascular lesions and secreting antifibrotic factors at different stages of disease"],"prefix":"10.1186","volume":"16","author":[{"given":"Ziyu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonghao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahui","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangguang","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiucun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"4470_CR1","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1016\/S0140-6736(17)30933-9","volume":"390","author":"CP Denton","year":"2017","unstructured":"Denton CP, Khanna D. Systemic sclerosis. Lancet Lond Engl. 2017;390:1685\u201399.","journal-title":"Lancet Lond Engl"},{"key":"4470_CR2","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/j.jaad.2021.10.065","volume":"87","author":"R Jerjen","year":"2022","unstructured":"Jerjen R, Nikpour M, Krieg T, Denton CP, Saracino AM. Systemic sclerosis in adults. Part I: clinical features and pathogenesis. J Am Acad Dermatol. 2022;87:937\u201354.","journal-title":"J Am Acad Dermatol"},{"key":"4470_CR3","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1007\/s12026-017-8926-y","volume":"65","author":"M Furue","year":"2017","unstructured":"Furue M, Mitoma C, Mitoma H, Tsuji G, Chiba T, Nakahara T, et al. Pathogenesis of systemic sclerosis\u2014current concept and emerging treatments. 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Title of the approved project: Effect and mechanism of ADRC in the treatment of scleroderma fibrosis. The mice were euthanized, in line with the national guidelines for euthanasia of laboratory animals (GB\/T 39760\u2009\u2212\u20092021). Clinical trial number: not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"328"}}