Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions

Static cold storage (SCS) remains the most widely used method of liver graft preservation due to its simplicity, accessibility, and reduced cost in transplantation practice. Since the invention of the University of Wisconsin (UW) solution, several alternative preservation solutions—including histidi...

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Autores: Panisello Roselló, Arnau, Carbonell i Camós, Teresa, Roselló Catafau, Juan, Vengohechea, Jordi, Hessheimer, Amelia, Adam, R. (René), Fondevila Campo, Constantino
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/224691
Acceso en línea:https://hdl.handle.net/2445/224691
Access Level:acceso abierto
Palabra clave:Mitocondris
Òxid nítric
Glicols
Estrès oxidatiu
Polietilè
Proteïnes quinases
Mitochondria
Nitric oxide
Glycols
Oxidative stress
Polyethylene
Protein kinases
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repository_id_str
spelling Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate SolutionsPanisello Roselló, ArnauCarbonell i Camós, TeresaRoselló Catafau, JuanVengohechea, JordiHessheimer, AmeliaAdam, R. (René)Fondevila Campo, ConstantinoMitocondrisÒxid nítricGlicolsEstrès oxidatiuPolietilèProteïnes quinasesMitochondriaNitric oxideGlycolsOxidative stressPolyethyleneProtein kinasesStatic cold storage (SCS) remains the most widely used method of liver graft preservation due to its simplicity, accessibility, and reduced cost in transplantation practice. Since the invention of the University of Wisconsin (UW) solution, several alternative preservation solutions—including histidine–tryptophan–ketoglutarate (HTK), Celsior, and more recently IGL-1 and IGL-2—have been formulated to optimize cellular and vascular protection during cold ischemia. More recently, the introduction of dynamic perfusion techniques, such as hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP), approximately fifteen years ago, has further enhanced transplantation protocols, being applied either alone or in combination with traditional SCS to ensure optimal graft preservation prior to implantation. Despite these technological advances, achieving fully effective dynamic perfusion remains a key challenge for improving outcomes in vulnerable grafts, particularly steatotic or marginal livers. This review details how Polyethylene Glycol 35 (PEG35)-based solutions activate multiple cytoprotective pathways during SCS, including AMP-activated protein kinase (AMPK), nitric oxide (NO) production, and the antioxidant transcription factor Nrf2. We propose that these molecular mechanisms serve as a form of preconditioning that is synergistically leveraged by HOPE to preserve mitochondrial function, endothelial glycocalyx integrity, and microvascular homeostasis. Furthermore, the oncotic and rheological properties of PEG35 reduce perfusate viscosity, mitigating shear stress and microcirculatory damage during dynamic perfusion—effects that are further enhanced by NO- and AMPK-mediated protection initiated during the SCS phase. This integrated approach provides a strong rationale for combining PEG35-mediated SCS with HOPE, particularly for grafts with high susceptibility to ischemia–reperfusion injury, such as fatty livers. Finally, we highlight emerging avenues in graft preservation, including the design of unified perfusion solutions that optimize endothelial, mitochondrial, and redox protection, with the potential to improve post-transplant outcomes and extend applicability to other solid organ grafts.MDPI2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/224691Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3390/ijms262311734International Journal of Molecular Sciences, 2025, vol. 26, num.23, p. 1-17https://doi.org/10.3390/ijms262311734cc-by (c) Panisello-Rosello, A. et al., 2025http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2246912026-05-27T06:46:51Z
dc.title.none.fl_str_mv Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
title Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
spellingShingle Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
Panisello Roselló, Arnau
Mitocondris
Òxid nítric
Glicols
Estrès oxidatiu
Polietilè
Proteïnes quinases
Mitochondria
Nitric oxide
Glycols
Oxidative stress
Polyethylene
Protein kinases
title_short Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
title_full Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
title_fullStr Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
title_full_unstemmed Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
title_sort Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
dc.creator.none.fl_str_mv Panisello Roselló, Arnau
Carbonell i Camós, Teresa
Roselló Catafau, Juan
Vengohechea, Jordi
Hessheimer, Amelia
Adam, R. (René)
Fondevila Campo, Constantino
author Panisello Roselló, Arnau
author_facet Panisello Roselló, Arnau
Carbonell i Camós, Teresa
Roselló Catafau, Juan
Vengohechea, Jordi
Hessheimer, Amelia
Adam, R. (René)
Fondevila Campo, Constantino
author_role author
author2 Carbonell i Camós, Teresa
Roselló Catafau, Juan
Vengohechea, Jordi
Hessheimer, Amelia
Adam, R. (René)
Fondevila Campo, Constantino
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Mitocondris
Òxid nítric
Glicols
Estrès oxidatiu
Polietilè
Proteïnes quinases
Mitochondria
Nitric oxide
Glycols
Oxidative stress
Polyethylene
Protein kinases
topic Mitocondris
Òxid nítric
Glicols
Estrès oxidatiu
Polietilè
Proteïnes quinases
Mitochondria
Nitric oxide
Glycols
Oxidative stress
Polyethylene
Protein kinases
description Static cold storage (SCS) remains the most widely used method of liver graft preservation due to its simplicity, accessibility, and reduced cost in transplantation practice. Since the invention of the University of Wisconsin (UW) solution, several alternative preservation solutions—including histidine–tryptophan–ketoglutarate (HTK), Celsior, and more recently IGL-1 and IGL-2—have been formulated to optimize cellular and vascular protection during cold ischemia. More recently, the introduction of dynamic perfusion techniques, such as hypothermic oxygenated perfusion (HOPE) and normothermic machine perfusion (NMP), approximately fifteen years ago, has further enhanced transplantation protocols, being applied either alone or in combination with traditional SCS to ensure optimal graft preservation prior to implantation. Despite these technological advances, achieving fully effective dynamic perfusion remains a key challenge for improving outcomes in vulnerable grafts, particularly steatotic or marginal livers. This review details how Polyethylene Glycol 35 (PEG35)-based solutions activate multiple cytoprotective pathways during SCS, including AMP-activated protein kinase (AMPK), nitric oxide (NO) production, and the antioxidant transcription factor Nrf2. We propose that these molecular mechanisms serve as a form of preconditioning that is synergistically leveraged by HOPE to preserve mitochondrial function, endothelial glycocalyx integrity, and microvascular homeostasis. Furthermore, the oncotic and rheological properties of PEG35 reduce perfusate viscosity, mitigating shear stress and microcirculatory damage during dynamic perfusion—effects that are further enhanced by NO- and AMPK-mediated protection initiated during the SCS phase. This integrated approach provides a strong rationale for combining PEG35-mediated SCS with HOPE, particularly for grafts with high susceptibility to ischemia–reperfusion injury, such as fatty livers. Finally, we highlight emerging avenues in graft preservation, including the design of unified perfusion solutions that optimize endothelial, mitochondrial, and redox protection, with the potential to improve post-transplant outcomes and extend applicability to other solid organ grafts.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/224691
url https://hdl.handle.net/2445/224691
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.3390/ijms262311734
International Journal of Molecular Sciences, 2025, vol. 26, num.23, p. 1-17
https://doi.org/10.3390/ijms262311734
dc.rights.none.fl_str_mv cc-by (c) Panisello-Rosello, A. et al., 2025
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Panisello-Rosello, A. et al., 2025
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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