{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:25:47Z","timestamp":1787664347241,"version":"build-2736575974"},"reference-count":68,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32230056"],"award-info":[{"award-number":["32230056"]}],"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":["32361163656"],"award-info":[{"award-number":["32361163656"]}],"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":["32471000"],"award-info":[{"award-number":["32471000"]}],"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":["U24A20378"],"award-info":[{"award-number":["U24A20378"]}],"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":["32230058"],"award-info":[{"award-number":["32230058"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["KG202511"],"award-info":[{"award-number":["KG202511"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2024300408"],"award-info":[{"award-number":["2024300408"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["XJ2024003602"],"award-info":[{"award-number":["XJ2024003602"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Thymic hypofunction due to primary defects, aging, infection, or cytoreductive therapies causes profound restriction of the T\u2010cell receptor (TCR) repertoire and increases rates of morbidity and mortality. Restoring thymic function is therefore critical. Here, the distinctive niche within the spleen has inspired the development of intrasplenic thymus regeneration (ISTR), an approach in which cultured thymic tissue fragments are implanted into the spleens of athymic nude mice, aged mice, thymectomized mice undergoing hematopoietic stem cell transplantation (HSCT), and humanized mice. The spleen's abundant vasculature and supportive stromal milieu enable rapid thymic organogenesis, leading to the reconstitution of phenotypically diverse and functional T\u2010cell compartments, as well as protective responses to viral and tumor challenges. Relative to intramuscular implantation, ISTR drives faster and more complete thymic development, generates greater T\u2010cell output, and is associated with a lower incidence of graft\u2010vs.\u2010host disease. In humanized animals, intrasplenic thymus grafts also promote the rapid emergence of functional human T cells. These results identify the spleen as an optimal ectopic niche for thymus regeneration and provide a promising strategy for clinical immune reconstitution and regenerative immunology.<\/jats:p>","DOI":"10.1002\/advs.77358","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:16:07Z","timestamp":1787663767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intrasplenic Thymus Organogenesis from Injectable Tissue Fragments Restores Functional T\u2010Cell Immunity"],"prefix":"10.1002","author":[{"given":"Shaocong","family":"Wang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Resource Center for Mutant Mice MOE Key Laboratory of Model Animal for Disease Study Model Animal Research Center Department of Oncology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fulin","family":"Dai","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen","family":"Xing","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"},{"name":"Wuxi Xishan Institute of Applied Biotechnology Nanjing University  Wuxi Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"},{"name":"Jiangsu Key Laboratory of Sericultural Biology and Biotechnology School of Biotechnology Jiangsu University of Science and Technology  Zhenjiang Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haochong","family":"Lei","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences &amp; Medicine King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7612-3953","authenticated-orcid":false,"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"National Resource Center for Mutant Mice MOE Key Laboratory of Model Animal for Disease Study Model Animal Research Center Department of Oncology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Wuxi Xishan Institute of Applied Biotechnology Nanjing University  Wuxi Jiangsu China"},{"name":"Chemistry and Biomedicine Innovation Center (ChemBIC) ChemBioMed Interdisciplinary Research Center at Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2013-4191","authenticated-orcid":false,"given":"Lei","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Sciences Nanjing University  Nanjing Jiangsu China"},{"name":"National Resource Center for Mutant Mice MOE Key Laboratory of Model Animal for Disease Study Model Animal Research Center Department of Oncology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University  Nanjing China"},{"name":"Wuxi Xishan Institute of Applied Biotechnology Nanjing University  Wuxi Jiangsu China"},{"name":"Chemistry and Biomedicine Innovation Center (ChemBIC) ChemBioMed Interdisciplinary Research Center at Nanjing University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(61)90693\u20106"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.123.1.75"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092\u20108674(87)90568\u2010X"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba2429"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010023\u201000911\u20108"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/imr.13306"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010024\u201001119\u20100"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2302892"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.14160"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2024.01.005"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trim.2022.101539"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.14173"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/v17030403"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010020\u201000457\u2010z"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2022017378"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.027"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202100543"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201020082\u20107"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592\u2010022\u201001583\u20103"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022\u20103476(98)70478\u20100"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199910143411603"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2017.03.020"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2007.11.009"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00383\u2010025\u201005976\u20101"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2021.06.028"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S379673"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201083378\u20104"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803364"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2009.03.004"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010018\u201008122\u20109"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12333"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202500849"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19051391"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aau6085"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz9974"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2006.06.016"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15530"},{"key":"e_1_2_11_39_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/978-3-031-77921-3_6","volume-title":"Thymus Transcriptome and Cell Biology","author":"Irla M.","year":"2025"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142143"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2023.03.015"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010019\u20100518\u20107"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.ade0182"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.148.6.1620"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590\u2010021\u201000927\u2010z"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201001\u2010071605"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2302019120"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12865"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00897"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102021\u2010325018"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305913"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adj9615"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102014\u201002\u2010555128"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10860"},{"key":"e_1_2_11_55_1","first-page":"1293","article-title":"The Critical Role of Lymph Nodes in Corneal Alloimmunization and Graft Rejection","volume":"42","author":"Yamagami S.","year":"2001","journal-title":"Investigative Ophthalmology and Visual Science"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.add3955"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2023.101732"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2024.10.009"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8558"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102249.2006.03310.x"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2012.05.007"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12026\u2010024\u201009519\u2010z"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3791\/906"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2022.101217"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.10.016"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2023.105787"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0736"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017204\u20105"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2015.06.011"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77358","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77358","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T13:16:08Z","timestamp":1787663768000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,25]]},"references-count":68,"alternative-id":["10.1002\/advs.77358"],"URL":"https:\/\/doi.org\/10.1002\/advs.77358","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,25]]},"assertion":[{"value":"2026-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77358"}}