{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T12:38:36Z","timestamp":1785155916357,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Organ Medicine"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The number of patients in need of a liver transplant far exceeds the supply of available organs. This imbalance could be dramatically reduced should the donor organ pool be expanded by rendering marginal cases transplantable rather than discarded. The poly\u2010pharmacological drug cocktail CEPT (Chroman\u20101, Emricasan, Polyamine, and Trans\u2010ISRIB [integrated stress inhibitor]) has been found to improve the in\u2010vitro viability of human pluripotent stem cells (hPSCs) following cryopreservation. It is worth exploring CEPT's ability to inhibit various apoptotic pathways and preserve cellular function for potentially mitigating warm ischemic stress of the anhepatic phase of graft implantation and promoting more rapid graft recovery following reperfusion with continuous treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Rat livers without warm ischemia and CEPT supplementation are the healthy control: fresh group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20093). Room\u2010temperature warm ischemia was used to replicate the anhepatic phase of graft implantation in the control group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) and the experimental CEPT group (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) without and with CEPT supplementation, respectively. Transplantation was modeled by ex vivo reperfusion at 37\u00b0C for 6\u2009h with William's E\u2010based hepatocyte culture media and with CEPT supplementation in the CEPT group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Livers treated with CEPT during warm ischemia and subsequent reperfusion have improved hepatocellular function as indicated by increased oxygen utilization, stable pH, and improved cholangiocyte function, indicated by the increased hourly rate of bile production. Furthermore, resistance, an endothelial injury marker, and caspase 3\/7, an apoptotic marker, were lower.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>To improve the utilization of available donor livers, different stages of the organ transplantation process can be optimized. The anhepatic phase, which includes the period from the removal of the native liver from the recipient to the reperfusion of the donor's graft liver through the portal vein during graft implantation, can be targeted using CEPT for mitigating warm ischemia\u2010induced injury that occurs during vascular anastomosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/orm2.70018","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:30:53Z","timestamp":1765758653000},"page":"141-152","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Optimization of Liver Graft Function Using the Poly\u2010Pharmacological Drug Cocktail CEPT in a Simulated Transplant Model"],"prefix":"10.1002","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6887-6224","authenticated-orcid":false,"given":"Anil","family":"Kharga","sequence":"first","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Department of Surgery Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Harvard Medical School Boston Massachusetts USA"},{"name":"Shriners Children's Boston Boston Massachusetts USA"},{"name":"Center for Transplantation Sciences, Department of Surgery Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Transplant Surgery, Penn Medicine University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9248-8550","authenticated-orcid":false,"given":"Huyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Department of Surgery Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Harvard Medical School Boston Massachusetts USA"},{"name":"Shriners Children's Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"McLean S.","family":"Taggart","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Department of Surgery Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Harvard Medical School Boston Massachusetts USA"},{"name":"Shriners Children's Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza","family":"Mojoudi","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Department of Surgery Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Harvard Medical School Boston Massachusetts USA"},{"name":"Shriners Children's Boston Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia T.","family":"Dinicu","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Department of Surgery Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Harvard 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