{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:41:29Z","timestamp":1785415289409,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100027448","name":"Catalyst","doi-asserted-by":"crossref","award":["CCG0280"],"award-info":[{"award-number":["CCG0280"]}],"id":[{"id":"10.13039\/100027448","id-type":"DOI","asserted-by":"crossref"}]},{"award":["CCG0280"],"award-info":[{"award-number":["CCG0280"]}],"id":[{"id":"https:\/\/ror.org\/00qvjvf51","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Uterus transplantation (UTx) is an emerging treatment for absolute uterine factor infertility. However, the use of deceased donors is limited, and donation after circulatory death (DCD) has not yet been utilized. Ischemic injury remains a major barrier, particularly compared with living donor procedures. Hypothermic oxygenated perfusion (HOPE), which has shown protective effects in heart, liver, and kidney transplantation, may offer similar benefits for uterine grafts. Methods: We report the first series applying HOPE to human uteri to improve preservation and enable metabolic injury assessment during perfusion. Six uteri (3 DBD, 3 DCD; median donor age 53 years) underwent 8 h of HOPE following procurement, while paired tissue controls were preserved using static cold storage (SCS). Perfusion was delivered using a pressure-controlled system (15 mmHg, 10 \u00b1 1 \u00b0C, VitaSmart\u00ae). Perfusate and tissue samples were analyzed for mitochondrial injury, inflammation, and transcriptional responses. Results: HOPE maintained stable flows (70\u2013150 mL\/min), delivered high oxygen levels (pO2 \u2248 1000 hPa), and increased tissue ATP levels. Stratification based on perfusate flavin mononucleotide (FMN) release identified grafts with greater Complex I\/II injury. HOPE was associated with lower levels of mitochondrial injury markers and inflammatory signals, preserved tissue architecture, and promoted gene expression patterns consistent with metabolic recovery compared with paired SCS tissue controls. Conclusions: These findings suggest that HOPE may serve as a preservation approach that enables metabolic and ischemic injury assessment and may facilitate broader use of deceased donor uteri for transplantation.<\/jats:p>","DOI":"10.3390\/jcm15082820","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T09:49:44Z","timestamp":1775641784000},"page":"2820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["First Experience with Hypothermic Oxygenated Perfusion in Human Uteri: Feasibility and Metabolic Characterization"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8928-4630","authenticated-orcid":false,"given":"Keyue","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasim","family":"Eshraghi","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1260-7005","authenticated-orcid":false,"given":"Fernanda Walsh","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeeta","family":"Satish","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"},{"name":"Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9566-8243","authenticated-orcid":false,"given":"Chunbao","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Selin","family":"Yildirim","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geofia","family":"Crasta","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4950-139X","authenticated-orcid":false,"given":"Omer F.","family":"Karakaya","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9930-1887","authenticated-orcid":false,"given":"Koki","family":"Takase","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Horie","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8609-4797","authenticated-orcid":false,"given":"Karen S.","family":"Keslar","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1791-504X","authenticated-orcid":false,"given":"Dylan","family":"Isaacson","sequence":"additional","affiliation":[{"name":"Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7271-1827","authenticated-orcid":false,"suffix":"3rd","given":"William","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Fairchild","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2327-6777","authenticated-orcid":false,"given":"Koji","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2972-3782","authenticated-orcid":false,"given":"Alejandro","family":"Pita","sequence":"additional","affiliation":[{"name":"Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin","family":"Wee","sequence":"additional","affiliation":[{"name":"Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariam","family":"AlHilli","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Miller","sequence":"additional","affiliation":[{"name":"Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Eltemamy","sequence":"additional","affiliation":[{"name":"Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Falcone","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology and Reproductive Biology, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Tzakis","sequence":"additional","affiliation":[{"name":"Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliot","family":"Richards","sequence":"additional","affiliation":[{"name":"Wake Forest Bapist Center for Fertility and Reproductive Surgery, Atrium Health, Winston Salem, NC 27103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Schlegel","sequence":"additional","affiliation":[{"name":"Department of Inflammation and Immunity, Cleveland Clinic Research Institute, Cleveland, OH 44195, USA"},{"name":"Transplantation Center, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1001\/jama.2024.11679","article-title":"Uterus Transplant in Women With Absolute Uterine-Factor Infertility","volume":"332","author":"Testa","year":"2024","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/aogs.15080","article-title":"A Decade of Human Uterus Transplantation","volume":"104","year":"2025","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0140-6736(14)61728-1","article-title":"Livebirth after Uterus Transplantation","volume":"385","author":"Johannesson","year":"2015","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2697","DOI":"10.1016\/S0140-6736(18)31766-5","article-title":"Livebirth after Uterus Transplantation from a Deceased Donor in a Recipient with Uterine Infertility","volume":"392","author":"Ejzenberg","year":"2018","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1111\/aogs.13853","article-title":"Live Birth after Robotic-Assisted Live Donor Uterus Transplantation","volume":"99","author":"Akouri","year":"2020","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Johannesson, L., Fischbach, C., Walker, O., and Testa, G. (2025). Past, Present, and Future: A Review of Uterus Transplant. Transpl. Int., 38.","DOI":"10.3389\/ti.2025.15325"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.fertnstert.2025.02.006","article-title":"Standardization of Robot-Assisted Living Donor Hysterectomy for Uterus Transplantation","volume":"124","author":"Tamate","year":"2025","journal-title":"Fertil. Steril."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1097\/TP.0000000000003578","article-title":"Uterine Transplantation: Review of Livebirths and Reproductive Implications","volume":"105","author":"Jones","year":"2021","journal-title":"Transplantation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1152\/physiol.00011.2024","article-title":"Uterus Transplantation: The Translational Evolution of a Clinical Breakthrough","volume":"39","author":"Adashi","year":"2024","journal-title":"Physiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.fertnstert.2019.05.029","article-title":"Live versus Deceased Donor in Uterus Transplantation","volume":"112","author":"Enskog","year":"2019","journal-title":"Fertil. 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Scand."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.jhep.2022.12.030","article-title":"A Multicenter Randomized-Controlled Trial of Hypothermic Oxygenated Perfusion (HOPE) for Human Liver Grafts before Transplantation","volume":"78","author":"Schlegel","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103014","DOI":"10.1016\/j.ebiom.2020.103014","article-title":"Hypothermic Oxygenated Perfusion Protects from Mitochondrial Injury before Liver Transplantation","volume":"60","author":"Schlegel","year":"2020","journal-title":"eBioMedicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1056\/NEJMoa0802289","article-title":"Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation","volume":"360","author":"Moers","year":"2009","journal-title":"N. Engl. J. 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