{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T21:03:57Z","timestamp":1789506237524,"version":"build-2803163510"},"reference-count":41,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2020YFA0710800"],"award-info":[{"award-number":["2020YFA0710800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071364"],"award-info":[{"award-number":["32071364"]}],"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":["32371419"],"award-info":[{"award-number":["32371419"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Umbilical cord\u2010derived mesenchymal stromal cells (MSCs) transplantation is a promising therapy for systemic sclerosis (SSc) because of their distinctive antifibrotic and immunomodulatory properties. To enhance the effects of MSCs transplantation, novel engineered MSC aggregates preconditioned with human E\/N\u2010cadherin fusion protein (hE\/N\u2010cad\u2010Fc) and interleukin\u20106 (IL\u20106) for SSc treatment are fabricated and named 3D\u2010Cad\/IL6\u2010MSCs. These novel\u2010engineered MSC aggregates possess tighter cellular cohesion and exhibit enhanced antiapoptotic, immunosuppressive, and proangiogenic capabilities according to transcriptomic analyses. Moreover, 3D\u2010Cad\/IL6\u2010MSCs have improved immunoregulatory effects on peripheral blood mononuclear cells (PBMCs), CD4<jats:sup>+<\/jats:sup> T cells, and CD8<jats:sup>+<\/jats:sup> T cells in vitro because of the synergistic preconditioning from IL\u20106 and bioactive hE\/N\u2010cad\u2010Fc. Upon intravenous injection, 3D\u2010Cad\/IL6\u2010MSCs significantly mitigate skin and lung fibrosis and prolong the retention duration in bleomycin (BLM)\u2010induced SSc mouse model. In detail, they suppress excessive infiltration of macrophages and T cells in the injured skin and lungs and reestablish the immune equilibrium of circulating CD4<jats:sup>+<\/jats:sup> T\u2010cell subsets in vivo. These results suggest that 3D\u2010Cad\/IL6\u2010MSCs are ideal candidates for SSc therapy and optimize the clinical utilization of MSCs.<\/jats:p>","DOI":"10.1002\/adhm.202500663","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T10:59:57Z","timestamp":1749725997000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Engineered MSC Aggregates with E\/N\u2010Cadherin and IL\u20106 Preconditioning for the Treatment of Systemic Sclerosis"],"prefix":"10.1002","volume":"14","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Jiangsu University  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyuan","family":"Qian","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Bioactive Materials, Ministry of Education College of Life Science Nankai University  94 Weijin Road Tianjin 300071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirui","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxu","family":"Cao","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Bioactive Materials, Ministry of Education College of Life Science Nankai University  94 Weijin Road Tianjin 300071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1220-8514","authenticated-orcid":false,"given":"Shanshan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School  321 Zhongshan Road Nanjing 210008 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Bioactive Materials, Ministry of Education College of Life Science Nankai University  94 Weijin Road Tianjin 300071 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8563-2036","authenticated-orcid":false,"given":"Lingyun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University  321 Zhongshan Road Nanjing 210008 P. R. China"},{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical University  218 Jixi Road Hefei 230022 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01692-0"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-023-00807-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2017.06.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-022-01264-2"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-021-08892-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.01.006"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202303349"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szad011"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121620"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201200373"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02822-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79664-6"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-021-00132-4"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2011-200955"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10020318"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2022.101765"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/C6TB00765A"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2013.03.042"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201600114"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.01.030"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202200246"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3802"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a003053"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-384289"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2018.01.002"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1986"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11051329"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2010.08.003"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2007.10.010"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05403-4"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01142"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.10410"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071049"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01612-y"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02404-8"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11020445"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020121"},{"key":"e_1_2_9_32_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903670"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-024-06865-z"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03002-y"},{"key":"e_1_2_9_34_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.181885"}],"container-title":["Advanced Healthcare Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/adhm.202500663","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T10:04:16Z","timestamp":1759745056000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/adhm.202500663"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,11]]},"references-count":41,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/adhm.202500663"],"URL":"https:\/\/doi.org\/10.1002\/adhm.202500663","archive":["Portico"],"relation":{},"ISSN":["2192-2640","2192-2659"],"issn-type":[{"value":"2192-2640","type":"print"},{"value":"2192-2659","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,11]]},"assertion":[{"value":"2025-02-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2500663"}}