{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T10:05:53Z","timestamp":1790244353820,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"53","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007899","name":"University of Arizona","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007899","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK132873"],"award-info":[{"award-number":["R01DK132873"]}],"id":[{"id":"10.13039\/100000002","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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Organoids derived from human induced pluripotent stem cells (iPSCs) serve as advanced multicellular models for studying human organ development and disease. Recent liver organoid platforms focus on achieving multicellular organization while minimizing reliance on xenogeneic extracellular matrices to support future clinical translation. Building on these advances, this study establishes a xenogeneic\u2010free strategy that develops the hepatic cellular repertoire with interdigitating vasculature using an air\u2010liquid interface approach, generating highly vascularized, multicellular, and functional liver organoids from de\u2010identified control and metabolic dysfunction\u2010associated steatohepatitis (MASH) donor\u2010derived iPSCs. Phenotypic and functional characterization confirms the presence of hepatocytes, cholangiocytes, stellate cells, sinusoidal endothelial cells, and Kupffer\u2010like cells. These organoids demonstrate the capacity to model steatohepatitis following free\u2010fatty acid exposure and predict acetaminophen\u2010induced drug toxicity. Organoids derived from MASH\u2010donors exhibit increased susceptibility to steatosis, inflammation, fibrosis, and acetaminophen\u2010induced toxicity. Lipidomic profiling reveals that MASH phenotype in organoids induces global lipidomic shifts that closely resemble those observed in MASH liver biopsies. Further post\u2010transplantation into mice, the organoids retain hepatic cell repertoire, establish functional anastomoses with host vasculature, display intraluminal erythrocytes, and secrete human\u2010specific albumin, validating their translational potential. This approach provides a robust, xenogeneic\u2010free platform for disease modeling, evaluating drug responses, and exploring regenerative therapies.<\/jats:p>","DOI":"10.1002\/advs.202521373","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T10:44:05Z","timestamp":1785149045000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MASH Background Confers Enhanced Disease Susceptibility and Acetaminophen Toxicity in iPSC\u2010Derived Liver Organoids"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9427-0244","authenticated-orcid":false,"given":"Ekta","family":"Minocha","sequence":"first","affiliation":[{"name":"Department of Surgery College of Medicine University of Arizona  Tucson Arizona USA"},{"name":"Bio5 Institute University of Arizona  Tucson Arizona USA"},{"name":"Surgery Service Southern Arizona VA Health Care System  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7069-5299","authenticated-orcid":false,"given":"Ashwani Kumar","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Surgery College of Medicine University of Arizona  Tucson Arizona USA"},{"name":"Bio5 Institute University of Arizona  Tucson Arizona USA"},{"name":"Surgery Service Southern Arizona VA Health Care System  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nate","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Bio5 Institute University of Arizona  Tucson Arizona USA"},{"name":"Department of Immunobiology University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5277-1997","authenticated-orcid":false,"given":"Richard M.","family":"Green","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7460-7567","authenticated-orcid":false,"given":"John G.","family":"Purdy","sequence":"additional","affiliation":[{"name":"Bio5 Institute University of Arizona  Tucson Arizona USA"},{"name":"Department of Immunobiology University of Arizona College of Medicine  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5680-1067","authenticated-orcid":false,"given":"Jason A.","family":"Wertheim","sequence":"additional","affiliation":[{"name":"Department of Surgery College of Medicine University of Arizona  Tucson Arizona USA"},{"name":"Bio5 Institute University of Arizona  Tucson Arizona USA"},{"name":"Surgery Service Southern Arizona VA Health Care System  Tucson Arizona USA"},{"name":"Department of Biomedical Engineering University of Arizona  Tucson Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.017"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2013.08.006"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010020\u20100259\u20103"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.11.050"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.06.010"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12271"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cels.2020.11.002"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.12.028"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010023\u201003235\u20105"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.030"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.05.007"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2024.122898"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.11.013"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxac090"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010023\u201001074\u20101"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3517"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tice.2019.101312"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002077107"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287\u2010018\u20100794\u20104"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.04.001"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2016.11.027"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/br.2015.480"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27165"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201026764\u20100"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.05.027"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2023.07.006"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201064195\u20101"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.11"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00322"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12876\u2010018\u20100789\u20108"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.12412"},{"key":"e_1_2_11_33_1","first-page":"60","article-title":"Ulex Europaeus I Lectin as a Marker for Vascular Endothelium in Human Tissues","volume":"47","author":"Holth\u00f6fer H.","year":"1982","journal-title":"Laboratory Investigation"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2021.100104"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.06.017"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.18053\/jctres.03.2017s1.006"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2012.09.008"},{"key":"e_1_2_11_38_1","first-page":"195","volume-title":"Advances in Pharmacology","author":"Ramachandran A.","year":"2019"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1101\/pdb.prot078089"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI.INSIGHT.94954"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.005"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.08.007"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29483"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010021\u201002910\u20108"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.0c00682"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010025\u201001416\u20106"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13578\u2010023\u201001136\u2010x"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.14440\/jbm.2021.357"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.15283\/ijsc20060"},{"key":"e_1_2_11_50_1","doi-asserted-by":"crossref","unstructured":"H. Y.Tsang P. H. Y.Lo andK. K. H.Lee \u201cGeneration of Liver Organoids From Human Induced Pluripotent Stem Cells as Liver Fibrosis and Steatosis Models \u201dBioRxiv 2021.06.29.450347https:\/\/doi.org\/10.1101\/2021.06.29.450347.","DOI":"10.1101\/2021.06.29.450347"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2007.09.014"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2015.01.009"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478\u20103231.2009.02111.x"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108455"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840150125"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2010.100"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.06.007"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1361084"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.02.034"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22796"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1242\/bio.055087"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.02.050"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2024.100601"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2023.1221669"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105484"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.003"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09342"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep46658"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2023.115621"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.156063"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201011278\u2010x"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00167\u201021"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00843\u201019"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201036298\u20102"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202521373","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.202521373","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202521373","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:18:31Z","timestamp":1790241511000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202521373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":73,"journal-issue":{"issue":"53","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/advs.202521373"],"URL":"https:\/\/doi.org\/10.1002\/advs.202521373","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]},"assertion":[{"value":"2025-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21373"}}