{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:48:13Z","timestamp":1788187693651,"version":"build-2803163510"},"reference-count":67,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"32","funder":[{"name":"National Research Foundation of Korea (NRF) grant","award":["RS-2021-NR061977 and No. RS-2026-25471704"],"award-info":[{"award-number":["RS-2021-NR061977 and No. RS-2026-25471704"]}]},{"name":"Korean Fund for Regenerative Medicine (KFRM) grant","award":["22A0101L1-11"],"award-info":[{"award-number":["22A0101L1-11"]}]},{"name":"Korea Basic Science Institute (National research Facilities and Equipment Center) grant","award":["RS-2025-00563046"],"award-info":[{"award-number":["RS-2025-00563046"]}]},{"name":"Korea US Collaborative Research Fund","award":["RS-2024-00468338"],"award-info":[{"award-number":["RS-2024-00468338"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,8,7]]},"abstract":"<jats:p>Liver tissue engineering offers a promising alternative for end-stage liver disease, yet the recreation of functional vasculature remains a major bottleneck to clinical translation. Here, we developed vascularized liver organoids by integrating human induced pluripotent stem cell (iPSC)\u2013derived hepatoblasts and endothelial cells into decellularized scaffolds functionalized with an anti-CD31 aptamer\u2013based vascular coating agent (VCA). This facilitated spatially coordinated organization of vasculature and parenchyma. Spatial transcriptomic profiling and subsequent functional perturbation demonstrated IGF2-IGF1R-AKT\/MAPK signaling as a key axis governing spatial organization and functional maturation of the liver organoids. Furthermore, exogenous IGF2 synergized with the VCA to augment the structural and functional refinement of liver organoids, which translated into markedly improved therapeutic outcomes following transplantation into a chronic liver failure mouse model. Collectively, these findings establish a comprehensive framework for generating physiologically relevant liver tissues from iPSCs and demonstrate the utility of spatial transcriptomics for uncovering regenerative mechanisms. This approach advances the feasibility of autologous, transplantable liver grafts for personalized regenerative therapy.<\/jats:p>","DOI":"10.1126\/sciadv.aea3814","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T18:01:42Z","timestamp":1785952902000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Leveraging IGF signaling to improve the spatial organization and regenerative potential of iPSC-derived vascularized liver organoids"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-0951","authenticated-orcid":true,"given":"Da-Hyun","family":"Kim","sequence":"first","affiliation":[{"name":"Adult Stem Cell Research Center and Research Institute for Veterinary Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea."},{"name":"Department of Biotechnology, Sungshin Women\u2019s University, Seoul 01133, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9958-221X","authenticated-orcid":true,"given":"Yongju","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7381-8696","authenticated-orcid":true,"given":"Min-Ji","family":"Kim","sequence":"additional","affiliation":[{"name":"Adult Stem Cell Research Center and Research Institute for Veterinary Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0350-7080","authenticated-orcid":true,"given":"Amos Chungwon","family":"Lee","sequence":"additional","affiliation":[{"name":"Meteor Biotech, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3514-1738","authenticated-orcid":true,"given":"Sunghoon","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9322-741X","authenticated-orcid":true,"given":"Kyung-Sun","family":"Kang","sequence":"additional","affiliation":[{"name":"Adult Stem Cell Research Center and Research Institute for Veterinary Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-02072-z"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13770-023-00576-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/20417314241286092"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2024.06.001"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2014.05.080"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-35941-2"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107711"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2015.0313"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.833163"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2016.04.042"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.07.046"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2023.1103727"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120417"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-021-00146-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-021-00370-8"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gpb.2020.02.005"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0739-1"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43458-x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03705-x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-018-1543-9"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30299-3"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7358"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119673"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz849"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.765980"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08850-1"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-023-01316-4"},{"key":"e_1_3_2_29_2","doi-asserted-by":"crossref","first-page":"208","DOI":"10.3390\/ijtm4020012","article-title":"Spatial computational hepatic molecular biomarker reveals LSEC role in midlobular liver zonation fibrosis in DILI and NASH liver injury","volume":"4","author":"Puri M.","year":"2024","unstructured":"M. Puri, Spatial computational hepatic molecular biomarker reveals LSEC role in midlobular liver zonation fibrosis in DILI and NASH liver injury. Int. J. Transl. Med. 4, 208\u2013223 (2024).","journal-title":"Int. J. Transl. Med."},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1530\/JME-14-0215"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-020-05339-0"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507865102"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12390"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.05.001"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49236-7"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0705"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-08-2955"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00048.2018"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-06-162891"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219079110"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-018-9627-4"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1478"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29340"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07376-2"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-0342-4"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909374107"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24067"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2170"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/adfm.201801954"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119283"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1088\/2053-1583\/ac6ba8"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.12.005"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-015-0180-2"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.11.019"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.02.005"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2017.04.006"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10112819"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40824-023-00348-z"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202411667"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-025-01416-6"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2024.10.015"},{"key":"e_1_3_2_62_2","doi-asserted-by":"crossref","unstructured":"M. Ogawa J. C. Liu A. Dadvar B. Tian X. Zhao I. Fernandes K. Minegishi K. Takase C. Cui M. Hernandez Y. Higuchi H. Suemizu I. McGilvray M. Parland G. Bader S. Ogawa Scalable expansion and hepatic zone maturation of hepatic progenitor cells from human pluripotent stem cells. bioRxiv 659636 [Preprint] (2025). https:\/\/doi.org\/10.1101\/2025.06.13.659636.","DOI":"10.1101\/2025.06.13.659636"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202302943"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-019-0109-9"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08677-w"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1177\/20417314241248753"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202400919"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04554-5"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aea3814","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T18:03:55Z","timestamp":1785953035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aea3814"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":67,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2026,8,7]]}},"alternative-id":["10.1126\/sciadv.aea3814"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aea3814","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]},"assertion":[{"value":"2025-07-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaea3814"}}