{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:18:36Z","timestamp":1788308316573,"version":"build-2803163510"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":15,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82572906"],"award-info":[{"award-number":["82572906"]}],"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":["82472565"],"award-info":[{"award-number":["82472565"]}],"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":["82302828"],"award-info":[{"award-number":["82302828"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2025-PUMCH-D-001"],"award-info":[{"award-number":["2025-PUMCH-D-001"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-C-025"],"award-info":[{"award-number":["2022-PUMCH-C-025"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-A-210"],"award-info":[{"award-number":["2022-PUMCH-A-210"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-019"],"award-info":[{"award-number":["2021-I2M-1-019"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2025-I2M-FGS-001"],"award-info":[{"award-number":["2025-I2M-FGS-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Localized scleroderma (LoS) is a fibrotic skin disorder characterized by excessive collagen deposition, leading to functional and cosmetic impairments. Mesenchymal stromal cells (MSCs) offer therapeutic potential through immunomodulation and tissue repair, but their clinical use is limited by donor variability and replicative senescence. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) present a promising alternative owing to their scalable production and rejuvenated phenotype.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We generated adipose-derived iMSCs (AD-iMSCs) from reprogrammed adipose-derived stem cells (ADSCs) and compared their therapeutic efficacy to primary ADSCs in vitro and in vivo. Functional assays including transcriptomic profiling, conditioned medium (CM) effects on fibrosis markers (\u03b1-SMA, TGF-\u03b2\/Smad), and angiogenesis were conducted. A bleomycin-induced murine LoS model was employed to assess AD-iMSC engraftment, collagen deposition, and microvascularization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>AD-iMSCs exhibited rejuvenated-like phenotype, with reduced senescence markers and enhanced proliferative capacity. AD-iMSC-derived conditioned medium (AD-iMSCs-CM) outperformed ADSC-derived conditioned medium (ADSC-CM) in promoting angiogenesis in vitro. In vivo, AD-iMSCs demonstrated superior persistence and therapeutic efficacy, notably decreasing dermal thickness and collagen density while promoting vascularization. Mechanistically, AD-iMSCs more effectively suppressed the TGF-\u03b2\/Smad2\/3 signaling and extracellular matrix (ECM) remodeling pathways compared to ADSCs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In conclusion, our findings provide a robust preliminary proof-of-concept demonstrating that iPSC-mediated reprogramming yields iMSCs with rejuvenated-like phenotype and a potent anti-fibrotic secretome. These data offer a valuable molecular and functional rationale for the prospective development of iMSC-based platforms to circumvent the expansion limitations and donor variability inherent to primary MSC therapies for fibrotic skin disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/stcltm\/szag063","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:47:29Z","timestamp":1782920849000},"source":"Crossref","is-referenced-by-count":0,"title":["MSCs derived from ADSC-reprogrammed iPSCs exhibit enhanced therapeutic potential for treating skin fibrosis."],"prefix":"10.1093","volume":"15","author":[{"given":"Liquan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingfei","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meili","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengzhou","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4312-6036","authenticated-orcid":false,"given":"Nanze","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiuzuo","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1800-1282","authenticated-orcid":false,"given":"Yue","family":"Huang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Common Mechanism Research for Major Diseases, Department of Medical Genetics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7942-0125","authenticated-orcid":false,"given":"Xiao","family":"Long","sequence":"additional","affiliation":[{"name":"Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences , Beijing, 100005,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"2026090120022505000_szag063-B1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.pcl.2018.04.002","article-title":"Scleroderma in children and adolescents: localized scleroderma and systemic sclerosis","volume":"65","author":"Li","year":"2018","journal-title":"Pediatr Clin North Am"},{"key":"2026090120022505000_szag063-B2","doi-asserted-by":"publisher","first-page":"101489","DOI":"10.1016\/j.berh.2020.101489","article-title":"Scleroderma mimics - clinical features and management","volume":"34","author":"Orteu","year":"2020","journal-title":"Best Pract Res Clin Rheumatol"},{"key":"2026090120022505000_szag063-B3","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1186\/s13287-023-03543-w","article-title":"Mesenchymal stem cell-based therapy for autoimmune-related fibrotic skin diseases\u2014systemic sclerosis and sclerodermatous graft-versus-host disease","volume":"14","author":"Yang","year":"2023","journal-title":"Stem Cell Res Ther"},{"key":"2026090120022505000_szag063-B4","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.biotechadv.2018.03.011","article-title":"Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells - a review","volume":"36","author":"Bacakova","year":"2018","journal-title":"Biotechnol Adv"},{"key":"2026090120022505000_szag063-B5","doi-asserted-by":"publisher","first-page":"e17610","DOI":"10.1371\/journal.pone.0017610","article-title":"Purified mesenchymal stem cells are an efficient source for iPS cell induction","volume":"6","author":"Niibe","year":"2011","journal-title":"PLoS ONE"},{"key":"2026090120022505000_szag063-B6","doi-asserted-by":"publisher","first-page":":881","DOI":"10.3390\/ijms24010881","article-title":"PSC-derived MSCs are a distinct entity of MSCs with higher therapeutic potential than their donor-matched parental MSCs","volume":"24","author":"Lee","year":"2023","journal-title":"IJMS"},{"key":"2026090120022505000_szag063-B7","doi-asserted-by":"publisher","first-page":"83","DOI":"10.5966\/sctm.2011-0022","article-title":"Small molecule mesengenic induction of human induced pluripotent stem cells to generate mesenchymal stem\/stromal cells","volume":"1","author":"Chen","year":"2012","journal-title":"Stem Cells Transl Med"},{"key":"2026090120022505000_szag063-B8","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nbt.2816","article-title":"Mesenchymal stem cells: immune evasive, not immune privileged","volume":"32","author":"Ankrum","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2026090120022505000_szag063-B9","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3389\/fimmu.2015.00560","article-title":"Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells","volume":"6","author":"Mattar","year":"2015","journal-title":"Front Immunol"},{"key":"2026090120022505000_szag063-B10","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1186\/s13287-024-03951-6","article-title":"Distinct muscle regenerative capacity of human induced pluripotent stem cell-derived mesenchymal stromal cells in Ullrich congenital muscular dystrophy model mice","volume":"15","author":"Yokomizo-Goto","year":"2024","journal-title":"Stem Cell Res Ther"},{"key":"2026090120022505000_szag063-B11","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1016\/j.stem.2025.05.004","article-title":"Diversifying the reference iPSC line concept","volume":"32","author":"Ellis","year":"2025","journal-title":"Cell Stem Cell"},{"key":"2026090120022505000_szag063-B12","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"2026090120022505000_szag063-B13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/s40824-023-00371-0","article-title":"Progress and emerging techniques for biomaterial-based derivation of mesenchymal stem cells (MSCs) from pluripotent stem cells (PSCs)","volume":"27","author":"Prakash","year":"2023","journal-title":"Biomater Res"},{"key":"2026090120022505000_szag063-B14","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1186\/s13287-019-1209-x","article-title":"Human iPSC-derived MSCs (iMSCs) from aged individuals acquire a rejuvenation signature","volume":"10","author":"Spitzhorn","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"2026090120022505000_szag063-B15","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1002\/stem.2993","article-title":"Induced pluripotent stem cell-derived mesenchymal stromal cells are functionally and genetically different from bone marrow-derived mesenchymal stromal cells","volume":"37","author":"Xu","year":"2019","journal-title":"Stem Cells (1981)"},{"key":"2026090120022505000_szag063-B16","doi-asserted-by":"publisher","first-page":"e12683","DOI":"10.1016\/j.heliyon.2022.e12683","article-title":"Comparative analysis of mesenchymal stem\/stromal cells derived from human induced pluripotent stem cells and the cognate umbilical cord mesenchymal stem\/stromal cells","volume":"9","author":"Wang","year":"2023","journal-title":"Heliyon"},{"key":"2026090120022505000_szag063-B17","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1161\/circulationaha.109.898312","article-title":"Functional mesenchymal stem cells derived from human induced pluripotent stem cells attenuate limb ischemia in mice","volume":"121","author":"Lian","year":"2010","journal-title":"Circulation"},{"key":"2026090120022505000_szag063-B18","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.stem.2009.08.021","article-title":"Generation of induced pluripotent stem cells from human cord blood","volume":"5","author":"Haase","year":"2009","journal-title":"Cell Stem Cell"},{"key":"2026090120022505000_szag063-B19","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1038\/cr.2011.12","article-title":"Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures","volume":"21","author":"Chou","year":"2011","journal-title":"Cell Res"},{"key":"2026090120022505000_szag063-B20","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1038\/nature09342","article-title":"Epigenetic memory in induced pluripotent stem cells","volume":"467","author":"Kim","year":"2010","journal-title":"Nature"},{"key":"2026090120022505000_szag063-B21","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1038\/nbt.2052","article-title":"Donor cell type can influence the epigenome and differentiation potential of human induced pluripotent stem cells","volume":"29","author":"Kim","year":"2011","journal-title":"Nat Biotechnol"},{"key":"2026090120022505000_szag063-B22","doi-asserted-by":"publisher","first-page":"15720","DOI":"10.1073\/pnas.0908450106","article-title":"Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells","volume":"106","author":"Sun","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026090120022505000_szag063-B23","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/nprot.2010.173","article-title":"Generation of adult human induced pluripotent stem cells using nonviral minicircle DNA vectors","volume":"6","author":"Narsinh","year":"2011","journal-title":"Nat Protoc"},{"key":"2026090120022505000_szag063-B24","doi-asserted-by":"publisher","first-page":"643125","DOI":"10.3389\/fcell.2021.643125","article-title":"Current advanced therapies based on human mesenchymal stem cells for skin diseases","volume":"9","author":"Sierra-S\u00e1nchez","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2026090120022505000_szag063-B25","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.stemcr.2019.12.012","article-title":"Senescence-Associated metabolomic phenotype in primary and iPSC-Derived mesenchymal stromal cells","volume":"14","author":"Fernandez-Rebollo","year":"2020","journal-title":"Stem Cell Reports"},{"key":"2026090120022505000_szag063-B26","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1002\/sctm.17-0305","article-title":"Mesenchymal stem cells (MSC) derived from induced pluripotent stem cells (iPSC) equivalent to adipose-derived MSC in promoting intestinal healing and microbiome normalization in mouse inflammatory bowel disease model","volume":"7","author":"Soontararak","year":"2018","journal-title":"Stem Cells Transl Med"},{"key":"2026090120022505000_szag063-B27","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1126\/science.282.5391.1145","article-title":"Embryonic stem cell lines derived from human blastocysts","volume":"282","author":"Thomson","year":"1998","journal-title":"Science"}],"container-title":["Stem Cells Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/9\/szag063\/70895860\/szag063.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/stcltm\/article-pdf\/15\/9\/szag063\/70895860\/szag063.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:02:34Z","timestamp":1788307354000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/stcltm\/article\/doi\/10.1093\/stcltm\/szag063\/8778744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,18]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,8,18]]}},"URL":"https:\/\/doi.org\/10.1093\/stcltm\/szag063","relation":{},"ISSN":["2157-6564","2157-6580"],"issn-type":[{"value":"2157-6564","type":"print"},{"value":"2157-6580","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,9]]},"published":{"date-parts":[[2026,8,18]]},"article-number":"szag063"}}