{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:14:48Z","timestamp":1785413688054,"version":"3.56.0"},"reference-count":86,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T00:00:00Z","timestamp":1784937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Foundation","award":["EEC 1,941,543"],"award-info":[{"award-number":["EEC 1,941,543"]}]},{"award":["EEC 1,941,543"],"award-info":[{"award-number":["EEC 1,941,543"]}],"id":[{"id":"https:\/\/ror.org\/021nxhr62","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Institute of Health","doi-asserted-by":"publisher","award":["5R01DK131543-03"],"award-info":[{"award-number":["5R01DK131543-03"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Institute of Health","doi-asserted-by":"publisher","award":["F32HL176334"],"award-info":[{"award-number":["F32HL176334"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Donor liver scarcity is exacerbated by preservation-related injury, particularly ischemia-reperfusion injury (IRI), which reduces organ utilization and increases discard rates. Liver sinusoidal endothelial cells (LSECs) play a critical role in mediating IRI, yet their response to static cold storage (SCS) remains poorly understood. Here, we investigate the impact of SCS on isolated rat LSECs. Isolated rat hepatocytes, stellate cells, Kupffer cells, and LSECs were subjected to up to 3 days of SCS followed by up to 2 days of recovery, with LSECs also receiving apoptosis and\/or oxidative stress inhibition. Afterwards, changes in survivability, functionality, and morphology were measured. Additionally, changes in gene, cytokine, and chemokine expression were also measured. We found that SCS reduced cell viability by approximately 40%, accompanied by a 60% reduction in metabolic activity and ATP levels, indicating substantial impairment in cellular energetics. SCS also doubled reactive oxygen species (ROS) production and upregulated oxidative stress and apoptosis-related genes, leading to functional decline in LSECs. Importantly, combined inhibition of apoptosis and oxidative stress improved LSEC viability by 20% and metabolic activity and ATP levels by 30% and 40%, respectively, and reduced ROS production by 50%. These findings highlight LSEC vulnerability to preservation injury and the importance of understanding LSEC-specific injury mechanisms to provide a foundation for the development of endothelial-targeted preservation strategies to significantly improve liver transplantation outcomes, subsequently increasing access to this life-saving treatment.<\/jats:p>","DOI":"10.3390\/cells15151334","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T01:26:23Z","timestamp":1785115583000},"page":"1334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oxidative Stress and Apoptosis Inhibition Mitigate Static Cold Storage-Induced Injury in Liver Sinusoidal Endothelial Cells"],"prefix":"10.3390","volume":"15","author":[{"given":"Bradley W.","family":"Ellis","sequence":"first","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Shriners Children\u2019s Boston, Boston, MA 02114, 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, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Shriners Children\u2019s Boston, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza","family":"Mojoudi","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Shriners Children\u2019s Boston, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alban","family":"Longchamp","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Yeh","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin L.","family":"Yarmush","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Shriners Children\u2019s Boston, Boston, MA 02114, USA"},{"name":"Department of Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3647-3665","authenticated-orcid":false,"given":"Mehmet","family":"Toner","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Shriners Children\u2019s Boston, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korkut","family":"Uygun","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Shriners Children\u2019s Boston, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basak E.","family":"Uygun","sequence":"additional","affiliation":[{"name":"Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"},{"name":"Shriners Children\u2019s Boston, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.2147\/DMSO.S146339","article-title":"Obesity and nonalcoholic fatty liver disease: Current perspectives","volume":"11","author":"Sarwar","year":"2018","journal-title":"Diabetes Metab. 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