{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:34:36Z","timestamp":1790307276181,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"43","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Modeling adaptive immune responses in induced pluripotent stem cell (iPSC)\u2010derived liver systems remains a critical barrier for studying immune\u2010mediated hepatic diseases, including idiosyncratic drug\u2010induced liver injury (iDILI). Conventional hepatotoxicity models lack the components required to capture patient\u2010specific, T cell\u2010mediated injury. Here, a scalable and matrix\u2010free human liver organoid (HLO) microarray platform is presented that enables controlled co\u2010culture of Human Leukocyte Antigen (HLA)\u2010genotyped, iPSC\u2010derived HLOs with autologous CD8\u207a T cells. This immune\u2010competent system supports antigen\u2010specific T cell activation and reproduces cytotoxic effector responses in a genetically defined context. As a proof\u2010of\u2010concept, the platform models clinically relevant iDILI caused by flucloxacillin in HLA\u2010B*57:01 carriers, recapitulating CD8\u207a T cell proliferation, hepatocyte apoptosis, and variability in immune responses across donors. The system captures hallmark features of adaptive immune\u2010mediated hepatotoxicity, including secretion of tumor necrosis factor\u2010alpha and Granzyme B, and cytokeratin\u201018 release from injured hepatocytes. By linking genetic susceptibility with functional immune outcomes, this platform provides a modular and scalable approach for evaluating immune\u2010mediated toxicities. The method offers broad utility for mechanistic studies of drug hypersensitivity, immune\u2010related adverse events, and preclinical safety assessment in support of precision medicine.<\/jats:p>","DOI":"10.1002\/advs.202508584","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T10:01:58Z","timestamp":1758880918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Autologous Organoid\u2010T Cell Co\u2010Culture Platform for Modeling of Immune\u2010Mediated Drug\u2010Induced Liver Injury"],"prefix":"10.1002","volume":"12","author":[{"given":"Fadoua El Abdellaoui","family":"Soussi","sequence":"first","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Brusilovsky","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Buck","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W Clark","family":"Bacon","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sina","family":"Dadgar","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Fullerton","sequence":"additional","affiliation":[{"name":"Genentech, Inc.  1 DNA Way South San Francisco CA 94080 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria Marsh","family":"Durban","sequence":"additional","affiliation":[{"name":"Molecular Devices LLC  San Jose CA 95134 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Barrile","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"},{"name":"Department of Biomedical Engineering College of Engineering and Applied Science of the University of Cincinnati  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Helmrath","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Takebe","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"},{"name":"Division of Gastroenterology Hepatology and Nutrition &amp; Division of Developmental Biology Cincinnati Children's Hospital Medical Center  Cincinnati OH 45229 USA"},{"name":"Premium Research Institute for Human Metaverse Medicine (WPI\u2010PRIMe), and Division of Stem Cell and Organoid Medicine The University of Osaka  Suita Osaka 565\u20130871 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Roth","sequence":"additional","affiliation":[{"name":"F. Hoffmann\u2010La Roche Ltd, Product Development, Precision Safety Roche Innovation Centre  Grenzacherstrasse 124 Basel 4070 Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Kasendra","sequence":"additional","affiliation":[{"name":"Center for Stem Cell and Organoid Medicine Cincinnati Children's Hospital Medical Center  Cincinnati OH 45219 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1816149"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1750"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfw177"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-014-8418-y"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15041300"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.10.002"},{"key":"e_1_2_9_7_1","first-page":"145","volume":"3","author":"Mak A.","year":"2017","journal-title":"J. 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