{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:09:23Z","timestamp":1790302163045,"version":"4.1.0"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"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":["U23A20516"],"award-info":[{"award-number":["U23A20516"]}],"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":["82304446"],"award-info":[{"award-number":["82304446"]}],"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":["82273897"],"award-info":[{"award-number":["82273897"]}],"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":["81922070"],"award-info":[{"award-number":["81922070"]}],"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":["82104281"],"award-info":[{"award-number":["82104281"]}],"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":["82300730"],"award-info":[{"award-number":["82300730"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Liver organoids have emerged as transformative tools for disease modeling and therapy development. However, their inability to form functional multivascular networks significantly limits their capacity to replicate the multifaceted functions of the native human liver with high fidelity. Here, novel vascularized liver organoids (3HLOs) are constructed by co\u2010culturing robust human reprogrammed hepatocyte\u2010like cells (hrHLs) with endothelial cells (HUVECs) and mesenchymal stem cells (HUMSCs) in a 3D system. After optimization, 3HLOs form vascular architecture featuring CD31\n                    <jats:sup>+<\/jats:sup>\n                    endothelial networks and CK19\n                    <jats:sup>+<\/jats:sup>\n                    biliary ducts, while demonstrating enhanced hepatic function, including upregulated glycogen storage, elevated albumin secretion, accelerated indocyanine green uptake, and improved rhodamine\u2010123 excretion. To improve physiological relevance, 3HLOs\u2010on\u2010chip models are developed for modeling alcohol\u2010induced liver injury (ALI) pathogenesis and testing hepatoprotective agents. The in vitro findings closely match in vivo observations, confirming the high physiological relevance of 3HLOs\u2010on\u2010chip ALI models. Subcutaneous implantation of 3HLOs significantly attenuated liver injury and promoted hepatic regeneration in end\u2010stage ALI mice, primarily through establishing functional anastomoses with host microvasculature. Multi\u2010omics analysis revealed that 3HLOs secreted human hepatoprotective proteins into the host circulating system, thereby modulating inflammatory responses and lipid metabolism pathways. Collectively, this work offers a robust and reliable platform for ALI modeling, drug testing, and liver regeneration.\n                  <\/jats:p>","DOI":"10.1002\/advs.202511169","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T11:40:01Z","timestamp":1764934801000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel Vascularized Human Liver Organoids for Modeling Alcohol\u2010Induced Liver Injury and Developing Hepatoprotective Therapy"],"prefix":"10.1002","volume":"13","author":[{"given":"Kangdi","family":"Yang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiayan","family":"Chu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuerui","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenkun","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinnuo","family":"Lu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuting","family":"Xu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoucheng","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoyu","family":"Pan","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Tsung","family":"Yang","sequence":"additional","affiliation":[{"name":"Future Industries Institute University of South Australia  Mawson Lakes Campus Adelaide SA 5095 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaojin","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaobin","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology Campus Virchow\u2010 Klinikum and Campus Charit\u00e9 Mitte Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin  13353 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-4349","authenticated-orcid":false,"given":"Guangbo","family":"Ge","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese Medicine  Shanghai 201203 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.030"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31653"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.05.046"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12271"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000343"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz6964"},{"key":"e_1_2_9_7_1","first-page":"17","volume":"11","author":"Zhang J. B.","year":"2024","journal-title":"Adv. Sci."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00411-3"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c08495"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122898"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i4.1348"},{"key":"e_1_2_9_12_1","first-page":"30","volume":"11","author":"Liu H. Y.","year":"2024","journal-title":"Adv. Sci."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00331-1"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31836"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.09.029"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41518-w"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2014.01.003"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2016.6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040812"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2015.08.043"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(03)00412-4"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2024.02.005"},{"key":"e_1_2_9_23_1","first-page":"95","volume":"14","author":"Tan F.","year":"2024","journal-title":"Signal Transduction Targeted Ther."},{"key":"e_1_2_9_24_1","first-page":"35","volume":"9","author":"Guo Z. B.","year":"2022","journal-title":"Adv. Sci."},{"key":"e_1_2_9_25_1","first-page":"8","volume":"6","author":"Guo Z. B.","year":"2022","journal-title":"Small Methods"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-013-0754-3"},{"key":"e_1_2_9_27_1","first-page":"1","volume":"30","author":"Liang H. T.","year":"2024","journal-title":"Mol. Med."},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122321"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.032"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0BM01221A"},{"key":"e_1_2_9_31_1","first-page":"17","volume":"13","author":"Pan Y. X.","year":"2024","journal-title":"Adv. Healthcare Mater."},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2023.03.013"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0359-5"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.005"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1598-0"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2011.03.004"},{"key":"e_1_2_9_37_1","first-page":"873","volume":"29","author":"Banfi A.","year":"2023","journal-title":"Tissue Eng., Part A"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107976"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063889"},{"key":"e_1_2_9_40_1","first-page":"1281","volume":"12","author":"Zhang Y. C.","year":"2021","journal-title":"Stem Cell Res. Ther."},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.26203"},{"key":"e_1_2_9_42_1","volume":"15","author":"Gao Y.","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-019-0242-8"},{"key":"e_1_2_9_44_1","first-page":"5","volume":"9","author":"Tao T. T.","year":"2022","journal-title":"Adv. Sci."},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3A0716-310R"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.02.028"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.10.010"},{"key":"e_1_2_9_48_1","first-page":"3207","volume":"14","author":"Hu Y. F.","year":"2025","journal-title":"Cells"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-023-01608-6"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1443297"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201507-468KV"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27024"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiu620"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32583"},{"key":"e_1_2_9_55_1","first-page":"194a","volume":"40","author":"Bowlus C. L.","year":"2004","journal-title":"Hepatology"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1002\/lt.25192"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2023.12.009"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-021-00279-y"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2025.02.042"},{"key":"e_1_2_9_60_1","first-page":"30","volume":"10","author":"Song Y. L.","year":"2023","journal-title":"Adv. Sci."},{"key":"e_1_2_9_61_1","first-page":"4 , 4","author":"Guo Z. B.","year":"2019","journal-title":"Adv. Mater. Technol."},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/am505051f"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511169","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202511169","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202511169","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:10:51Z","timestamp":1770970251000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202511169"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":62,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/advs.202511169"],"URL":"https:\/\/doi.org\/10.1002\/advs.202511169","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,5]]},"assertion":[{"value":"2025-06-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e11169"}}