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April 10, 2026Journal of Clinical Medicine2 citationsOpen Access

First Experience with Hypothermic Oxygenated Perfusion in Human Uteri: Feasibility and Metabolic Characterization

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KSKeyue SunCleveland ClinicNENasim EshraghiCleveland ClinicFFFernanda Walsh FernandesCleveland Clinic

Key Points

  • To explore the feasibility of hypothermic oxygenated perfusion (HOPE) in human uteri and assess its impact on metabolic injury.
  • Applied HOPE to six human uteri with varying donor conditions (DBD and DCD) for 8 hours.
  • Used a pressure-controlled system for perfusion at specified conditions and compared with static cold storage (SCS) controls.
  • Analyzed perfusate and tissue for injury and inflammation markers, and assessed metabolic responses.
  • Maintained stable perfusion flows with high oxygen levels during HOPE.
  • Increased ATP levels in tissue and identified injury through flavin mononucleotide release.
  • Demonstrated lower mitochondrial injury and inflammation levels compared to SCS, alongside preserved tissue structure.

Abstract

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 ± 1 °C, VitaSmart®). Perfusate and tissue samples were analyzed for mitochondrial injury, inflammation, and transcriptional responses. Results: HOPE maintained stable flows (70–150 mL/min), delivered high oxygen levels (pO2 ≈ 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.

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Cite This Study

Sun et al. (2026) studied this question.

synapsesocial.com/papers/69d895796c1944d70ce06753https://doi.org/10.3390/jcm15082820
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