2. Academic Validation
  3. UW supplementation with AP39 improves liver viability following static cold storage

UW supplementation with AP39 improves liver viability following static cold storage

  • Sci Rep. 2025 Jan 10;15(1):1559. doi: 10.1038/s41598-025-85302-w.
McLean Taggart 1 2,  Saige Holkup 1,  Alexandra Tchir 1 2 3,  Mohammadreza Mojoudi 1 2,  Arnaud Lyon 1 2,  Madeeha Hassan 1 2,  Christopher Taveras 1 2,  Ozge Sila Ozgur 1 2,  James F Markmann 4,  Heidi Yeh 1 5,  Korkut Uygun # 6 7,  Alban Longchamp # 8 9 10
Affiliations

Affiliations

  • 1 Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  • 2 Shriners Children's Boston, Boston, MA, USA.
  • 3 Massachusetts Institute of Technology, Boston, MA, USA.
  • 4 Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA, USA.
  • 5 Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA.
  • 6 Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. [email protected].
  • 7 Shriners Children's Boston, Boston, MA, USA. [email protected].
  • 8 Center for Engineering in Medicine and Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. [email protected].
  • 9 Shriners Children's Boston, Boston, MA, USA. [email protected].
  • 10 Center for Transplantation Sciences, Massachusetts General Hospital, Boston, MA, USA. [email protected].
  • # Contributed equally.
PMID: 39789174 DOI: 10.1038/s41598-025-85302-w
Abstract

Static cold storage of donor livers at 4 °C incompletely arrests metabolism, ultimately leading to decreases in ATP levels, oxidative stress, cell death, and organ failure. Hydrogen Sulfide (H2S) is an endogenously produced gas, previously demonstrated to reduce oxidative stress, reduce ATP depletion, and protect from ischemia and reperfusion injury. H2S is difficult to administer due to its rapid release curve, resulting in cellular death at high concentrations. AP39, a mitochondrially targeted, slow-release H2S donor, has been shown to reduce ischemia-reperfusion injury in hearts and kidneys. Thus, we investigated whether the addition of AP39 during 3-day static cold storage can improve liver graft viability. At the end of storage, livers underwent six hours of acellular normothermic machine perfusion, a model of transplantation. During simulated transplantation, livers stored with AP39 showed reduced resistance, reduced cellular damage (ALT and AST), and reduced Apoptosis. Additionally, bile production and glucose, as well as energy charge were improved by the addition of AP39. These results indicate that AP39 supplementation improves liver viability during static cold storage.

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