{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:48:06Z","timestamp":1777510086847,"version":"3.51.4"},"reference-count":40,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Republic of T\u00fcrkiye Ministry of National Education"},{"DOI":"10.13039\/501100009127","name":"Invention for Innovation Programme","doi-asserted-by":"publisher","award":["(ref. II-C3-0714-2003)"],"award-info":[{"award-number":["(ref. II-C3-0714-2003)"]}],"id":[{"id":"10.13039\/501100009127","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>\n                    Liver transplantation is the only curative option for end-stage liver disease, but its applicability is limited by donor shortages. Hepatocyte transplantation offers a promising alternative, particularly for pediatric acute liver failure, yet its success relies on the availability of viable cells. Cryopreservation enables off-the-shelf use, though long-term storage may impair cell quality. This study investigates whether cryostorage duration, donor characteristics, and organ retrieval parameters affect the viability and functionality of cryopreserved primary human hepatocytes (PHHs). We conducted a retrospective analysis of 144 thawing events across 81 GMP-grade hepatocyte batches, cryopreserved for up to 14 years. Donor age ranged from 3 days to 70 years. Viability and functionality were assessed using MTT assays, albumin and urea secretion, and CYP450 activity. Linear regression was used to analyze correlations (\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.05 considered significant). The cryopreservation duration had no significant impact on hepatocyte viability or function, confirming that clinical-grade PHHs can maintain quality for up to 14 years. However, donor age correlated negatively with post-thaw viability (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.035,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.029), yield (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.039,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.041), and metabolic activity (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.278,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.008), while showing a positive correlation with induced ethoxy resorufin O-demethylation (EROD) function (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.432,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.020). Donor body mass index (BMI) showed significant negative associations with viability (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.075,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.003), yield (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.069,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.011), and metabolic activity (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.267,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.019). Cold ischemia time (CIT) showed a weak negative correlation with viability (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    = 0.151,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    &lt; 0.0001), particularly when CIT exceeded ~10 h and viability fell below 60%. Clinical-grade cryopreserved hepatocytes retain viability and function for over a decade. CIT, donor BMI, and age impacted post-thaw quality, while warm ischemia time (WIT), within our current criteria, and storage duration had minimal impact. These findings support refining donor selection to improve cryopreservation outcomes.\n                  <\/jats:p>","DOI":"10.1177\/09636897261417050","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:05:13Z","timestamp":1776661513000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cryopreservation of hepatocytes: Impact of long-term storage and organ donor factors on cell quality for clinical applications"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4720-4864","authenticated-orcid":false,"given":"Kadriye","family":"G\u00fcven","sequence":"first","affiliation":[{"name":"DhawanLab, Institute of Liver Studies, King\u2019s College London, King\u2019s College Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Iansante","sequence":"additional","affiliation":[{"name":"DhawanLab, Institute of Liver Studies, King\u2019s College London, King\u2019s College Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharon C.","family":"Lehec","sequence":"additional","affiliation":[{"name":"DhawanLab, Institute of Liver Studies, King\u2019s College London, King\u2019s College Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ragai R.","family":"Mitry","sequence":"additional","affiliation":[{"name":"DhawanLab, Institute of Liver Studies, King\u2019s College London, King\u2019s College Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil","family":"Dhawan","sequence":"additional","affiliation":[{"name":"DhawanLab, Institute of Liver Studies, King\u2019s College London, King\u2019s College Hospital, London, UK"},{"name":"Paediatric Liver, GI and Nutrition Centre, King\u2019s College London, King\u2019s College Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4679-3275","authenticated-orcid":false,"given":"C\u00e9line","family":"Filippi","sequence":"additional","affiliation":[{"name":"DhawanLab, Institute of Liver Studies, King\u2019s College London, King\u2019s College Hospital, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2019.12.005"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.44"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2017.284"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13312-016-0795-2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/lt.24433"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.02.040"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-022-03674-3"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.12.002"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.09.014"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1600-6143.2003.00310.x"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1159\/000369552"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000351332"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2013.10.042"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i2.874"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3727\/000000007783464821"},{"issue":"1","key":"e_1_3_3_17_2","first-page":"1","article-title":"Exploring donor demographics effects on hepatocyte yield and viability: results of whole human liver isolation from one center","volume":"7","author":"Geerts S","year":"2019","unstructured":"Geerts S, Ozer S, Chu C, Fuchs BC, Tanabe KK, Yeh H, Uygun K. 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Hepatocyte cryopreservation: is it time to change the strategy? World J Gastroenterol. 2010;16(1):1\u201314.","journal-title":"World J Gastroenterol"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897261417050","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09636897261417050","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09636897261417050","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:36:24Z","timestamp":1777390584000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09636897261417050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4]]},"references-count":40,"alternative-id":["10.1177\/09636897261417050"],"URL":"https:\/\/doi.org\/10.1177\/09636897261417050","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4]]},"article-number":"09636897261417050"}}