{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T13:30:04Z","timestamp":1772199004772,"version":"3.50.1"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK114506, R01DK096075, R01DK107875"],"award-info":[{"award-number":["R01DK114506, R01DK096075, R01DK107875"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK114506, R01DK096075, R01DK107875"],"award-info":[{"award-number":["R01DK114506, R01DK096075, R01DK107875"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK114506, R01DK096075, R01DK107875"],"award-info":[{"award-number":["R01DK114506, R01DK096075, R01DK107875"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK114506, R01DK096075, R01DK107875"],"award-info":[{"award-number":["R01DK114506, R01DK096075, R01DK107875"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK114506, R01DK096075, R01DK107875"],"award-info":[{"award-number":["R01DK114506, R01DK096075, R01DK107875"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK114506, R01DK096075, R01DK107875"],"award-info":[{"award-number":["R01DK114506, R01DK096075, R01DK107875"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"},{"name":"U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The global shortage of donor organs has made it crucial to deeply understand and better predict donor liver viability. However, biomarkers that effectively assess viability of marginal grafts for organ transplantation are currently lacking. Here, we showed that hepatocytes, sinusoidal endothelial, stellate, and liver-specific immune cells were released into perfusates from Lewis rat livers as a result of cold ischemia and machine perfusion. Perfusate comparison analysis of fresh livers and cold ischemic livers showed that the released cell profiles were significantly altered by the duration of cold ischemia. Our findings show for the first time that parenchymal cells are released from organs under non-proliferative pathological conditions, correlating with the degree of ischemic injury. Thus, perfusate cell profiles could serve as potential biomarkers of graft viability and indicators of specific injury mechanisms during organ handling and transplantation. Further, parenchymal cell release may have applications in other pathological conditions beyond organ transplantation.<\/jats:p>","DOI":"10.1038\/s41598-020-57589-4","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T11:03:17Z","timestamp":1579863797000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cell release during perfusion reflects cold ischemic injury in rat livers"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4741-0686","authenticated-orcid":false,"given":"Reinier J.","family":"de Vries","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casie A.","family":"Pendexter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie E. J.","family":"Cronin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Marques","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1551-4309","authenticated-orcid":false,"given":"Ehab O. A.","family":"Hafiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alona","family":"Muzikansky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas M.","family":"van Gulik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James F.","family":"Markmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon L.","family":"Stott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Toner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2088-7860","authenticated-orcid":false,"given":"Korkut","family":"Uygun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2373-232X","authenticated-orcid":false,"given":"Shannon N.","family":"Tessier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"key":"57589_CR1","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.jhep.2018.09.014","volume":"70","author":"SK Asrani","year":"2019","unstructured":"Asrani, S. K., Devarbhavi, H., Eaton, J. & Kamath, P. S. Burden of liver diseases in the world. J. Hepatol. 70, 151\u2013171 (2019).","journal-title":"J. Hepatol."},{"key":"57589_CR2","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1111\/ajt.15276","volume":"19","author":"WR Kim","year":"2019","unstructured":"Kim, W. R. et al. OPTN\/SRTR 2017 Annual Data Report: Liver. Am. J. Transplant. 19, 184\u2013283 (2019).","journal-title":"Am. J. Transplant."},{"key":"57589_CR3","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1038\/nbt.3889","volume":"35","author":"S Giwa","year":"2017","unstructured":"Giwa, S. et al. The promise of organ and tissue preservation to transform medicine. Nat. Biotechnol. 35, 530\u2013542 (2017).","journal-title":"Nat. Biotechnol."},{"key":"57589_CR4","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1097\/01.sla.0000103063.82181.2c","volume":"239","author":"PL Abt","year":"2004","unstructured":"Abt, P. L. et al. Survival following liver transplantation from non-heart-beating donors. Ann. Surg. 239, 87\u201392 (2004).","journal-title":"Ann. Surg."},{"key":"57589_CR5","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1111\/j.1600-6143.2006.01242.x","volume":"6","author":"S Feng","year":"2006","unstructured":"Feng, S. et al. Characteristics Associated with Liver Graft Failure: The Concept of a Donor Risk Index. Am. J. Transplant. 6, 783\u2013790 (2006).","journal-title":"Am. J. Transplant."},{"key":"57589_CR6","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1002\/lt.24799","volume":"23","author":"A Flores","year":"2017","unstructured":"Flores, A. & Asrani, S. K. The donor risk index: A decade of experience. Liver Transpl. 23, 1216\u20131225 (2017).","journal-title":"Liver Transpl."},{"key":"57589_CR7","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1007\/s40472-018-0178-9","volume":"5","author":"CJE Watson","year":"2018","unstructured":"Watson, C. J. E. & Jochmans, I. From \u2018Gut Feeling\u2019 to Objectivity: Machine Preservation of the Liver as a Tool to Assess Organ Viability. Curr. Transplant. Rep. 5, 72\u201381 (2018).","journal-title":"Curr. Transplant. Rep."},{"key":"57589_CR8","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1007\/s40472-018-0186-9","volume":"5","author":"CDL Ceresa","year":"2018","unstructured":"Ceresa, C. D. L., Nasralla, D. & Jassem, W. Normothermic Machine Preservation of the Liver: State of the Art. Curr. Transplant. Rep. 5, 104\u2013110 (2018).","journal-title":"Curr. Transplant. Rep."},{"issue":"6","key":"57589_CR9","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1053\/j.gastro.2018.12.037","volume":"156","author":"Phillipp Dutkowski","year":"2019","unstructured":"Dutkowski, P. et al. Evolving Trends in Machine Perfusion for Liver Transplantation. Gastroenterology, https:\/\/doi.org\/10.1053\/j.gastro.2018.12.037 (2019).","journal-title":"Gastroenterology"},{"key":"57589_CR10","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1002\/lt.24751","volume":"23","author":"H Marecki","year":"2017","unstructured":"Marecki, H. et al. Liver ex situ machine perfusion preservation: A review of the methodology and results of large animal studies and clinical trials. Liver Transpl. 23, 679\u2013695 (2017).","journal-title":"Liver Transpl."},{"key":"57589_CR11","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/lt.24369","volume":"22","author":"T Perera","year":"2016","unstructured":"Perera, T. et al. First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion. Liver Transpl. 22, 120\u2013124 (2016).","journal-title":"Liver Transpl."},{"key":"57589_CR12","doi-asserted-by":"publisher","first-page":"S4","DOI":"10.1002\/cld.147","volume":"2","author":"M Krishna","year":"2013","unstructured":"Krishna, M. Microscopic anatomy of the liver. Clin. Liver Dis. 2, S4\u2013S7 (2013).","journal-title":"Clin. Liver Dis."},{"key":"57589_CR13","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1016\/j.cell.2016.02.048","volume":"164","author":"X Fan","year":"2016","unstructured":"Fan, X. & Rudensky, A. Y. Hallmarks of Tissue-Resident Lymphocytes. Cell 164, 1198\u20131211 (2016).","journal-title":"Cell"},{"key":"57589_CR14","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/ni.2691","volume":"14","author":"CN Jenne","year":"2013","unstructured":"Jenne, C. N. & Kubes, P. Immune surveillance by the liver. Nat. Immunol. 14, 996\u20131006 (2013).","journal-title":"Nat. Immunol."},{"key":"57589_CR15","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s00795-003-0229-9","volume":"37","author":"K Nakatani","year":"2004","unstructured":"Nakatani, K., Kaneda, K., Seki, S. & Nakajima, Y. Pit cells as liver-associated natural killer cells: morphology and function. Med. Electron Microsc. Off. J. Clin. Electron Microsc. Soc. Jpn. 37, 29\u201336 (2004).","journal-title":"Med. Electron Microsc. Off. J. Clin. Electron Microsc. Soc. Jpn."},{"key":"57589_CR16","doi-asserted-by":"crossref","unstructured":"Eltzschig, H. K. & Eckle, T. Ischemia and reperfusion\u2014from mechanism to translation. Nat. Med. 17 (2011).","DOI":"10.1038\/nm.2507"},{"key":"57589_CR17","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nri3561","volume":"14","author":"D Wallach","year":"2014","unstructured":"Wallach, D., Kang, T.-B. & Kovalenko, A. Concepts of tissue injury and cell death in inflammation: a historical perspective. Nat. Rev. Immunol. 14, 51\u201359 (2014).","journal-title":"Nat. Rev. Immunol."},{"key":"57589_CR18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.cytogfr.2012.04.006","volume":"23","author":"RF van Golen","year":"2012","unstructured":"van Golen, R. F., van Gulik, T. M. & Heger, M. The sterile immune response during hepatic ischemia\/reperfusion. Cytokine Growth Factor Rev. 23, 69\u201384 (2012).","journal-title":"Cytokine Growth Factor Rev."},{"key":"57589_CR19","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/ajt.13062","volume":"15","author":"ZA Stewart","year":"2015","unstructured":"Stewart, Z. A. UW Solution: Still the \u2018Gold Standard\u2019 for Liver Transplantation. Am. J. Transplant. 15, 295\u2013296 (2015).","journal-title":"Am. J. Transplant."},{"key":"57589_CR20","doi-asserted-by":"publisher","first-page":"775","DOI":"10.5301\/ijao.5000250","volume":"36","author":"BG Bruinsma","year":"2013","unstructured":"Bruinsma, B. G., Berendsen, T. A., Izamis, M.-L., Yarmush, M. L. & Uygun, K. Determination and extension of the limits to static cold storage using subnormothermic machine perfusion. Int. J. Artif. Organs 36, 775\u2013780 (2013).","journal-title":"Int. J. Artif. Organs"},{"key":"57589_CR21","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1038\/nm.3588","volume":"20","author":"TA Berendsen","year":"2014","unstructured":"Berendsen, T. A. et al. Supercooling enables long-term transplantation survival following 4 days of liver preservation. Nat. Med. 20, 790\u2013793 (2014).","journal-title":"Nat. Med."},{"key":"57589_CR22","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.ymthe.2017.08.019","volume":"26","author":"JLS Willoughby","year":"2018","unstructured":"Willoughby, J. L. S. et al. Evaluation of GalNAc-siRNA Conjugate Activity in Pre-clinical Animal Models with Reduced Asialoglycoprotein Receptor Expression. Mol. Ther. 26, 105\u2013114 (2018).","journal-title":"Mol. Ther."},{"key":"57589_CR23","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1042\/bj20030932","volume":"376","author":"A Hrzenjak","year":"2003","unstructured":"Hrzenjak, A. et al. Galactose-specific asialoglycoprotein receptor is involved in lipoprotein (a) catabolism. Biochem. J. 376, 765\u2013771 (2003).","journal-title":"Biochem. J."},{"key":"57589_CR24","unstructured":"Tissue expression of ASGR1 - Staining in liver - The Human Protein Atlas, https:\/\/www.proteinatlas.org\/ENSG00000141505-ASGR1\/tissue\/liver."},{"key":"57589_CR25","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1002\/hep.23085","volume":"50","author":"S March","year":"2009","unstructured":"March, S., Hui, E. E., Underhill, G. H., Khetani, S. & Bhatia, S. N. Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro. Hepatol. Baltim. Md 50, 920\u2013928 (2009).","journal-title":"Hepatol. Baltim. Md"},{"key":"57589_CR26","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1089\/ten.tec.2014.0152","volume":"21","author":"SS Bale","year":"2015","unstructured":"Bale, S. S. et al. Long-Term Coculture Strategies for Primary Hepatocytes and Liver Sinusoidal Endothelial Cells. Tissue Eng. Part C Methods 21, 413\u2013422 (2015).","journal-title":"Tissue Eng. Part C Methods"},{"key":"57589_CR27","doi-asserted-by":"publisher","first-page":"3078","DOI":"10.1074\/jbc.M405411200","volume":"280","author":"SK Meurer","year":"2005","unstructured":"Meurer, S. K., Tihaa, L., Lahme, B., Gressner, A. M. & Weiskirchen, R. Identification of Endoglin in Rat Hepatic Stellate Cells NEW INSIGHTS INTO TRANSFORMING GROWTH FACTOR \u03b2 RECEPTOR SIGNALING. J. Biol. Chem. 280, 3078\u20133087 (2005).","journal-title":"J. Biol. Chem."},{"key":"57589_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/srep44356","volume":"7","author":"O Strauss","year":"2017","unstructured":"Strauss, O., Phillips, A., Ruggiero, K., Bartlett, A. & Dunbar, P. R. Immunofluorescence identifies distinct subsets of endothelial cells in the human liver. Sci. Rep. 7, 44356 (2017).","journal-title":"Sci. Rep."},{"key":"57589_CR29","first-page":"2200","volume":"185","author":"MK Connolly","year":"2010","unstructured":"Connolly, M. K. et al. In Hepatic Fibrosis, Liver Sinusoidal Endothelial Cells Acquire Enhanced Immunogenicity. J. Immunol. Baltim. Md 1950 185, 2200\u20132208 (2010).","journal-title":"J. Immunol. Baltim. Md 1950"},{"key":"57589_CR30","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1111\/j.1443-9573.2005.00208.x","volume":"6","author":"DK Qiu","year":"2005","unstructured":"Qiu, D. K., Hua, J., Li, J. Q. & Li, E. L. CD14 expression on Kupffer cells during the course of carbon tetrachloride-mediated liver injury. Chin. J. Dig. Dis. 6, 137\u2013141 (2005).","journal-title":"Chin. J. Dig. Dis."},{"key":"57589_CR31","doi-asserted-by":"publisher","first-page":"622","DOI":"10.3748\/wjg.v9.i3.622","volume":"9","author":"L-L Dai","year":"2003","unstructured":"Dai, L.-L. et al. Synthesis of endotoxin receptor CD14 protein in Kupffer cells and its role in alcohol-induced liver disease. World J. Gastroenterol. 9, 622\u2013626 (2003).","journal-title":"World J. Gastroenterol."},{"key":"57589_CR32","doi-asserted-by":"publisher","first-page":"G640","DOI":"10.1152\/ajpgi.00253.2001","volume":"283","author":"GL Su","year":"2002","unstructured":"Su, G. L. et al. Activation of human and mouse Kupffer cells by lipopolysaccharide is mediated by CD14. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G640\u2013645 (2002).","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"57589_CR33","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1189\/JLB.0309135","volume":"86","author":"B Gao","year":"2009","unstructured":"Gao, B., Radaeva, S. & Park, O. Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases. J. Leukoc. Biol. 86, 513\u2013528 (2009).","journal-title":"J. Leukoc. Biol."},{"key":"57589_CR34","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/cmi.2015.96","volume":"13","author":"H Peng","year":"2016","unstructured":"Peng, H., Wisse, E. & Tian, Z. Liver natural killer cells: subsets and roles in liver immunity. Cell. Mol. Immunol. 13, 328\u2013336 (2016).","journal-title":"Cell. Mol. Immunol."},{"key":"57589_CR35","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1136\/gut.52.2.307","volume":"52","author":"AH Lau","year":"2003","unstructured":"Lau, A. H. & Thomson, A. W. Dendritic cells and immune regulation in the liver. Gut 52, 307\u2013314 (2003).","journal-title":"Gut"},{"key":"57589_CR36","doi-asserted-by":"publisher","first-page":"e110642","DOI":"10.1371\/journal.pone.0110642","volume":"9","author":"ME Sutton","year":"2014","unstructured":"Sutton, M. E. et al. Criteria for viability assessment of discarded human donor livers during ex vivo normothermic machine perfusion. PloS One 9, e110642 (2014).","journal-title":"PloS One"},{"key":"57589_CR37","doi-asserted-by":"publisher","first-page":"e28518","DOI":"10.1371\/journal.pone.0028518","volume":"6","author":"S Perk","year":"2011","unstructured":"Perk, S. et al. A metabolic index of ischemic injury for perfusion-recovery of cadaveric rat livers. PloS One 6, e28518 (2011).","journal-title":"PloS One"},{"key":"57589_CR38","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.cryobiol.2004.01.010","volume":"48","author":"S Jain","year":"2004","unstructured":"Jain, S. et al. Ex-vivo study of flow dynamics and endothelial cell structure during extended hypothermic machine perfusion preservation of livers. Cryobiology 48, 322\u2013332 (2004).","journal-title":"Cryobiology"},{"key":"57589_CR39","doi-asserted-by":"publisher","DOI":"10.1186\/2047-1440-1-6","volume":"1","author":"TA Berendsen","year":"2012","unstructured":"Berendsen, T. A. et al. A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation. Transplant. Res. 1, 6 (2012).","journal-title":"Transplant. Res."},{"key":"57589_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/srep22415","volume":"6","author":"BG Bruinsma","year":"2016","unstructured":"Bruinsma, B. G. et al. Metabolic profiling during ex vivo machine perfusion of the human liver. Sci. Rep. 6, 22415 (2016).","journal-title":"Sci. Rep."},{"key":"57589_CR41","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1111\/ajt.12727","volume":"14","author":"BG Bruinsma","year":"2014","unstructured":"Bruinsma, B. G. et al. Subnormothermic Machine Perfusion for Ex Vivo Preservation and Recovery of the Human Liver for Transplantation: Subnormothermic Machine Perfusion of Human Livers. Am. J. Transplant. 14, 1400\u20131409 (2014).","journal-title":"Am. J. Transplant."},{"key":"57589_CR42","doi-asserted-by":"publisher","first-page":"1637","DOI":"10.1097\/TP.0000000000001699","volume":"101","author":"BG Bruinsma","year":"2017","unstructured":"Bruinsma, B. G. et al. Peritransplant Energy Changes and Their Correlation to Outcome After Human Liver Transplantation. Transplantation 101, 1637\u20131644 (2017).","journal-title":"Transplantation"},{"key":"57589_CR43","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1002\/hep.1840360633","volume":"36","author":"K Vajdov\u00e1","year":"2002","unstructured":"Vajdov\u00e1, K., Graf, R. & Clavien, P.-A. ATP-supplies in the cold-preserved liver: A long-neglected factor of organ viability. Hepatol. Baltim. Md 36, 1543\u20131552 (2002).","journal-title":"Hepatol. Baltim. Md"},{"key":"57589_CR44","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1136\/gut.50.4.571","volume":"50","author":"H Reynaert","year":"2002","unstructured":"Reynaert, H., Thompson, M. G., Thomas, T. & Geerts, A. Hepatic stellate cells: role in microcirculation and pathophysiology of portal hypertension. Gut 50, 571\u2013581 (2002).","journal-title":"Gut"},{"key":"57589_CR45","doi-asserted-by":"publisher","first-page":"294","DOI":"10.2174\/157488810793351721","volume":"5","author":"U Erdbruegger","year":"2010","unstructured":"Erdbruegger, U., Dhaygude, A., Haubitz, M. & Woywodt, A. Circulating endothelial cells: markers and mediators of vascular damage. Curr. Stem Cell Res. Ther. 5, 294\u2013302 (2010).","journal-title":"Curr. Stem Cell Res. Ther."},{"key":"57589_CR46","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1097\/PAF.0b013e31823d29ad","volume":"33","author":"DK Molina","year":"2012","unstructured":"Molina, D. K. & DiMaio, V. J. M. Normal organ weights in men: part II-the brain, lungs, liver, spleen, and kidneys. Am. J. Forensic Med. Pathol. 33, 368\u2013372 (2012).","journal-title":"Am. J. Forensic Med. Pathol."},{"key":"57589_CR47","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/B978-0-12-394309-5.00006-7","volume":"298","author":"T Kalogeris","year":"2012","unstructured":"Kalogeris, T., Baines, C. P., Krenz, M. & Korthuis, R. J. Cell Biology of Ischemia\/Reperfusion Injury. Int. Rev. Cell Mol. Biol. 298, 229\u2013317 (2012).","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"57589_CR48","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/j.tiv.2006.06.003","volume":"20","author":"A-K Sohlenius-Sternbeck","year":"2006","unstructured":"Sohlenius-Sternbeck, A.-K. Determination of the hepatocellularity number for human, dog, rabbit, rat and mouse livers from protein concentration measurements. Toxicol. Vitro Int. J. Publ. Assoc. BIBRA 20, 1582\u20131586 (2006).","journal-title":"Toxicol. Vitro Int. J. Publ. Assoc. BIBRA"},{"key":"57589_CR49","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1002\/hep.510280201","volume":"28","author":"P-A Clavien","year":"1998","unstructured":"Clavien, P.-A. Sinusoidal endothelial cell injury during hepatic preservation and reperfusion. Hepatology 28, 281\u2013285 (1998).","journal-title":"Hepatology"},{"key":"57589_CR50","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1002\/hep.21887","volume":"46","author":"DB Stolz","year":"2007","unstructured":"Stolz, D. B. et al. Sinusoidal endothelial cell repopulation following ischemia\/reperfusion injury in rat liver transplantation. Hepatology 46, 1464\u20131475 (2007).","journal-title":"Hepatology"},{"key":"57589_CR51","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1007\/s10353-015-0363-3","volume":"48","author":"T Miyashita","year":"2016","unstructured":"Miyashita, T. et al. Ischemia reperfusion-facilitated sinusoidal endothelial cell injury in liver transplantation and the resulting impact of extravasated platelet aggregation. Eur. Surg. 48, 92\u201398 (2016).","journal-title":"Eur. Surg."},{"key":"57589_CR52","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1002\/lt.22172","volume":"16","author":"NM Jameel","year":"2010","unstructured":"Jameel, N. M. et al. Constitutive release of powerful antioxidant-scavenging activity by hepatic stellate cells: Protection of hepatocytes from ischemia\/reperfusion injury. Liver Transpl. 16, 1400\u20131409 (2010).","journal-title":"Liver Transpl."},{"key":"57589_CR53","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1016\/j.jhep.2013.09.013","volume":"60","author":"RK Stewart","year":"2014","unstructured":"Stewart, R. K. et al. A novel mouse model of depletion of stellate cells clarifies their role in ischemia\/reperfusion- and endotoxin-induced acute liver injury. J. Hepatol. 60, 298\u2013305 (2014).","journal-title":"J. Hepatol."},{"key":"57589_CR54","doi-asserted-by":"publisher","first-page":"10512","DOI":"10.3748\/wjg.v22.i48.10512","volume":"22","author":"C-Y Zhang","year":"2016","unstructured":"Zhang, C.-Y., Yuan, W.-G., He, P., Lei, J.-H. & Wang, C.-X. Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets. World J. Gastroenterol. 22, 10512\u201310522 (2016).","journal-title":"World J. Gastroenterol."},{"key":"57589_CR55","doi-asserted-by":"crossref","unstructured":"Magee, N., Zou, A. & Zhang, Y. Pathogenesis of Nonalcoholic Steatohepatitis: Interactions between Liver Parenchymal and Nonparenchymal Cells. BioMed Res. Int. 2016 (2016).","DOI":"10.1155\/2016\/5170402"},{"key":"57589_CR56","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1097\/TP.0000000000002193","volume":"102","author":"F Tacke","year":"2018","unstructured":"Tacke, F. New Insights on the Role of Kupffer Cells in Liver Transplantation. Transplantation 102, 896 (2018).","journal-title":"Transplantation"},{"key":"57589_CR57","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1016\/j.jhep.2014.04.031","volume":"61","author":"CJ Verhoeven","year":"2014","unstructured":"Verhoeven, C. J. et al. Biomarkers to assess graft quality during conventional and machine preservation in liver transplantation. J. Hepatol. 61, 672\u2013684 (2014).","journal-title":"J. Hepatol."},{"key":"57589_CR58","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1111\/j.1600-6143.2012.04086.x","volume":"12","author":"SD Henry","year":"2012","unstructured":"Henry, S. D. et al. Hypothermic machine preservation reduces molecular markers of ischemia\/reperfusion injury in human liver transplantation. Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg. 12, 2477\u20132486 (2012).","journal-title":"Am. J. Transplant. Off. J. Am. Soc. Transplant. Am. Soc. Transpl. Surg."},{"issue":"4","key":"57589_CR59","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3390\/metabo7040058","volume":"7","author":"Gautham Sridharan","year":"2017","unstructured":"Sridharan, G. V. et al. Metabolomic Modularity Analysis (MMA) to Quantify Human Liver Perfusion Dynamics. Metabolites 7 (2017).","journal-title":"Metabolites"},{"key":"57589_CR60","doi-asserted-by":"publisher","first-page":"14","DOI":"10.5500\/wjt.v9.i1.14","volume":"9","author":"YL Boteon","year":"2019","unstructured":"Boteon, Y. L. & Afford, S. C. Machine perfusion of the liver: Which is the best technique to mitigate ischaemia-reperfusion injury? World J. Transplant. 9, 14\u201320 (2019).","journal-title":"World J. Transplant."},{"key":"57589_CR61","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nprot.2014.044","volume":"9","author":"NM Karabacak","year":"2014","unstructured":"Karabacak, N. M. et al. Microfluidic, marker-free isolation of circulating tumor cells from blood samples. Nat. Protoc. 9, 694\u2013710 (2014).","journal-title":"Nat. Protoc."},{"key":"57589_CR62","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1053\/j.gastro.2018.09.020","volume":"155","author":"I Bhan","year":"2018","unstructured":"Bhan, I. et al. Detection and Analysis of Circulating Epithelial Cells in Liquid Biopsies From Patients With Liver Disease. Gastroenterology 155, 2016\u20132018.e11 (2018).","journal-title":"Gastroenterology"},{"key":"57589_CR63","doi-asserted-by":"publisher","DOI":"10.1038\/srep25329","volume":"6","author":"SS Bale","year":"2016","unstructured":"Bale, S. S., Geerts, S., Jindal, R. & Yarmush, M. L. Isolation and co-culture of rat parenchymal and non-parenchymal liver cells to evaluate cellular interactions and response. Sci. Rep. 6, 25329 (2016).","journal-title":"Sci. Rep."},{"key":"57589_CR64","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1021\/bp00009a007","volume":"7","author":"JC Dunn","year":"1991","unstructured":"Dunn, J. C., Tompkins, R. G. & Yarmush, M. L. Long-term in vitro function of adult hepatocytes in a collagen sandwich configuration. Biotechnol. Prog. 7, 237\u2013245 (1991).","journal-title":"Biotechnol. Prog."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57589-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57589-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57589-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T06:17:01Z","timestamp":1670307421000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-57589-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,24]]},"references-count":64,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["57589"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-57589-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,24]]},"assertion":[{"value":"20 June 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare competing interests. Drs. Toner, Uygun, Stott,\u00a0de Vries, and Tessier have provisional patent applications relevant to this study. Dr. Uygun has a financial interest in Organ Solutions, a company focused on developing organ preservation technology. All competing interests are managed by the MGH and Partners HealthCare in accordance with their conflict of interest policies.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1102"}}