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Molecular Insights into Transplantation and Machine Perfusion
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Molecular Insights into Transplantation and Machine Perfusion

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 March 2026) | Viewed by 3314

Special Issue Editors

Prof. Dr. Joan Roselló-Catafau

E-Mail Website
Guest Editor
Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Catalonia, Spain
Interests: liver transplantation; inflammation; ischemia reperfusion injury
Special Issues, Collections and Topics in MDPI journals
Dr. Arnau Panisello-Roselló

E-Mail Website
Guest Editor
Experimental Pathology Department, Institut d’Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC)-IDIBAPS, CIBEREHD, 08036 Barcelona, Catalonia, Spain
Interests: liver transplantation; fatty liver; ubiquitin proteasome; liver; proteasome; liver diseases; transplantation; organ transplantation; organ donation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Organ transplantation is the most effective therapy to prevent patient death. While organ transplantation is a successful story, the inherent growing demand for transplantable organs poses a crucial challenge to solve in clinical transplantation. This shortage necessitates the taking advantage of suboptimal organs, such as those from donors after circulatory death (DCD), and steatosis. These organs are highly vulnerable to ischemia-reperfusion injury, which is inherent to organ retrieval, washout, and preservation before transplantation. The combination of preserving the organ quality and those damaging events can lead to primary graft dysfunction, delayed graft function, or late biliary complications; all of them are limiting factors for the graft’s viability and even to leading to transplant rejection.

Therefore, optimal preservation of the graft is essential for improving transplant outcomes. To achieve this, it is not only necessary to enhance cold preservation strategies but also to employ dynamic perfusion strategies with machine perfusion. This has been successfully implemented in clinical practice for the liver and kidney by using Hypothermic Oxygenated Perfusion (HOPE) and Normothermic Machine Perfusion (NMP), which help maintain graft integrity until transplantation. This new approach may significantly increase the pool of usable grafts, improve outcomes for recipients, and enhance the utilization of suboptimal organs.

In this Special Issue entitled “Molecular Insights into Transplantation and Machine Perfusion” we highlight research and novel therapeutic strategies aimed at achieving optimal graft preservation for transplantation, with a special focus on the liver, kidney, and other organs.  This Special Issue will also include the development of new effluents/perfusates for optimizing the combination of cold static storage with HOPE and NMP ones in experimental and clinical settings. Metabolomic studies and graft pharmacological interventions are also welcome.

Prof. Dr. Joan Roselló-Catafau
Dr. Arnau Panisello-Roselló
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • transplantation (liver, kidney, and other organs)
  • primary failure
  • ischemia-reperfusion injury
  • static graft preservation
  • HOPE
  • NMP
  • cell signaling
  • glycocalyx
  • metabolomics
  • mitochondria
  • sterile inflammation

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Published Papers (2 papers)

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Research

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18 pages, 2398 KB  
Article
Extended Preservation of Heart Grafts: LYPS Solution Maintains Cardiac Function During 20-Hour Static Cold Storage
by Marie Védère, Evan Faure, Christophe Chouabe, Lionel Augeul, Ninon Cadot-Jet, Georges Christé, Yanis Charouit, Mégane Lo Grasso, Alexandre Ravon, Régine Cartier, Gabriel Bidaux, René Ferrera, Hala Guedouari and Delphine Baetz
Int. J. Mol. Sci. 2025, 26(22), 11170; https://doi.org/10.3390/ijms262211170 - 19 Nov 2025
Viewed by 793
Abstract
Heart transplantation is severely limited by the shortage of suitable donor grafts, partly due to myocardial vulnerability to ischemia–reperfusion injury and the lack of standardized preservation strategies. Current solutions only partially maintain myocardial viability, compromising post-transplant function. To address this issue, we made [...] Read more.
Heart transplantation is severely limited by the shortage of suitable donor grafts, partly due to myocardial vulnerability to ischemia–reperfusion injury and the lack of standardized preservation strategies. Current solutions only partially maintain myocardial viability, compromising post-transplant function. To address this issue, we made further improvements to our preservation solution, LYPS (Lyon Preservation Solution), based on mitochondrial metabolic activation and the limitation of membrane depolarization. We first evaluated commonly used extracellular solutions (Celsior and St. Thomas (ST)) on cardiac cell lines (H9C2) exposed to 20 h of cold (4 °C) simulated ischemia followed by 2 h of simulated reperfusion. In parallel, the same three solutions were compared in isolated pig hearts subjected to 20 h of cold static storage followed by reperfusion, with a group directly reperfused with blood at 37 °C serving as the control. Heart function was assessed using a non-working heart preparation, while mitochondrial functions and electrophysiological analysis were evaluated via biopsies and isolated cardiomyocytes. LYPS provided superior protection against cell death and mitochondrial membrane potential loss in vitro, outperformed ST in preserving mitochondrial function, and limited troponin I release by the heart. During reperfusion, LYPS-treated hearts showed improved functional recovery and contractility and better rhythmicity with almost no defibrillation requirements. These effects may involve the modulation of the repolarizing IK1 current. Overall, LYPS effectively preserves myocardial viability and function, representing a promising strategy to enhance graft quality during long-term cold preservation, even through using cold static storage. Full article
(This article belongs to the Special Issue Molecular Insights into Transplantation and Machine Perfusion)
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Review

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17 pages, 1415 KB  
Review
Static Cold Storage and Machine Perfusion: Redefining the Role of Preservation and Perfusate Solutions
by Arnau Panisello-Rosello, Teresa Carbonell, Joan Rosello-Catafau, Jordi Vengohechea, Amelia Hessheimer, René Adam and Constantino Fondevila
Int. J. Mol. Sci. 2025, 26(23), 11734; https://doi.org/10.3390/ijms262311734 - 4 Dec 2025
Cited by 1 | Viewed by 1629
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Molecular Insights into Transplantation and Machine Perfusion)
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