{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:03:03Z","timestamp":1791241383331,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,2,8]],"date-time":"2025-02-08T00:00:00Z","timestamp":1738972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0108201"],"award-info":[{"award-number":["2018YFA0108201"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515110940"],"award-info":[{"award-number":["2021A1515110940"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    To date, generating viable and functional hepatocytes in large scale remains challenge. By employing 3D suspension condition with the support of low concentration Matrigel, a novel culture system was developed to generate expandable hepatoblast organoids (HB\u2010orgs) and mature polarised hepatocyte organoids (P\u2010hep\u2010orgs) from human embryonic stem cells (hESCs) in both dishes and bioreactors. scRNA\u2010seq and functional assays were used to characterise HB\u2010orgs and P\u2010hep\u2010orgs. hESC\u2010derived HB\u2010orgs could proliferate at least for 15 passages, leading to 10\n                    <jats:sup>12<\/jats:sup>\n                    in total cells in 4\u2009weeks. P\u2010hep\u2010orgs differentiated from HB\u2010orgs displayed characteristics of mature hepatocytes with polarisation. Moreover, single\u2010cell RNA sequencing exhibited that over 40% of cells in P\u2010hep\u2010orgs were highly fidelity with human primary hepatocytes. Eventually, large\u2010scale production of P\u2010hep\u2010orgs could be generated from massively expanded HB\u2010orgs within 1\u2009week with similar number in bioreactors, which were achieved by the enhancements in energy metabolism contribute to the expansion of HB\u2010orgs and maturation of P\u2010hep\u2010orgs in bioreactors. By providing a cost\u2010efficient and robust platform, our study represents a significant step toward manufacturing large\u2010scale functioning hESC\u2010derived hepatocytes for cell\u2010based therapeutics, disease modelling, pharmacology and toxicology studies.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70001","type":"journal-article","created":{"date-parts":[[2025,2,9]],"date-time":"2025-02-09T06:58:41Z","timestamp":1739084321000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Large\u2010Scale Production of Expandable Hepatoblast Organoids and Polarised Hepatocyte Organoids From\n                    <scp>hESCs<\/scp>\n                    Under\n                    <scp>3D<\/scp>\n                    Static and Dynamic Suspension Conditions"],"prefix":"10.1111","volume":"58","author":[{"given":"Haibin","family":"Wu","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cells and Translational 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