Article
Multidisciplinary Sciences
Ngee-Soon Lau, Mark Ly, Claude Dennis, Andrew Jacques, Marti Cabanes-Creus, Shamus Toomath, Joanna Huang, Nicole Mestrovic, Paul Yousif, Sumon Chanda, Chuanmin Wang, Leszek Lisowski, Ken Liu, James G. Kench, Geoffrey McCaughan, Michael Crawford, Carlo Pulitano
Summary: Long-term machine perfusion of human livers outside the body is an emerging field with tremendous potential for the assessment, recovery, and modification of organs prior to transplantation. Here, the authors report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Silke B. Bodewes, Otto B. van Leeuwen, Adam M. Thorne, Bianca Lascaris, Rinse Ubbink, Ton Lisman, Diethard Monbaliu, Vincent E. De Meijer, Maarten W. N. Nijsten, Robert J. Porte
Summary: Oxygenated ex situ machine perfusion of donor livers is an alternative method for static cold preservation. Oxygen delivery is crucial for preserving organ viability, although challenging. Different oxygen carriers have their own advantages and disadvantages in organ preservation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Zhiyong Guo, Liqiang Zhan, Ningxin Gao, Zhiheng Zhang, Shanzhou Huang, Linhe Wang, Caihui Zhu, Zehua Jia, Meixian Yin, Fangcong Li, Shirui Chen, Tao Luo, Yao Liu, Yu Jia, Tielong Wang, Jinghong Xu, Yuexin Li, Yifan Zhu, Yichao Chen, Chuhan Yu, Yunhua Tang, Qiang Zhao, Dongping Wang, Xiaoshun He
Summary: This study compared the metabolism activities of donor livers between in situ and ex situ conditions during ischemia-free liver transplantation. Common and distinct metabolites were identified, indicating suppressed urea cycle pathway and more active metabolism in standard criteria donor group. These findings provide insights for improving perfusion device design, perfusate components, and graft viability criteria.
Article
Immunology
Siavash Raigani, John Santiago, Anders Ohman, Megan Heaney, Sofia Baptista, Taylor M. Coe, Reinier J. de Vries, Ivy Rosales, Angela Shih, James F. Markmann, Philip Gruppuso, Korkut Uygun, Jennifer Sanders, Heidi Yeh
Summary: The introduction of machine perfusion technology allows surgeons to monitor liver function before transplantation, and using specific therapeutic methods during machine perfusion can improve the quality of donated livers. In this study, targeting the apoptosis pathway showed potential in improving hepatocellular function and reducing immune and inflammatory responses, resulting in better transplant outcomes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Surgery
Qiang Liu, Luca Del Prete, Khaled Ali, Patrick Grady, Mary Bilancini, John Etterling, Giuseppe D'Amico, Teresa Diago Uso, Koji Hashimoto, Federico Aucejo, Masato Fujiki, Bijan Eghtesad, Kazunari Sasaki, Choon Hyuck David Kwon, Sulemon Chaudhry, Junshi Doi, Alejandro Pita, Brandon New, Ana Bennett, Jacek Cywinski, Charles Miller, Cristiano Quintini
Summary: The purpose of this study was to assess the safety and feasibility of sequential hypothermic oxygenated perfusion and normothermic machine perfusion and the potential benefits of graft viability preservation and assessment before liver transplantation. 17 expanded criteria donor livers underwent sequential hypothermic oxygenated perfusion and normothermic machine perfusion. The results showed that sequential hypothermic oxygenated perfusion and normothermic machine perfusion preservation is safe and feasible and has the potential benefits of preserving and evaluating expanded criteria donor livers.
Article
Biotechnology & Applied Microbiology
Melanie Kruger, Alicia Ruppelt, Benjamin Kappler, Elke Van Soest, Roos Anne Samsom, Guy C. M. Grinwis, Niels Geijsen, J. Bernd Helms, Marco Stijnen, Linda M. Kock, Marco Rasponi, Hans S. Kooistra, Bart Spee
Summary: This study established a feasible large animal model for studying liver diseases by collecting porcine livers in a slaughterhouse and perfusing them in vitro. The model allows for the investigation of metabolic and toxic liver disorders in the early stages and the observation of biochemical markers and functional impairment of liver damage. It provides a reliable alternative to experimental animals for studying liver diseases and potential treatments.
BIOENGINEERING-BASEL
(2022)
Article
Surgery
Richard X. Sousa Da Silva, Lucia Bautista Borrego, Daniela Lenggenhager, Florian Huwyler, Jonas Binz, Leandro Mancina, Eva Breuer, Kendra Wernle, Max Hefti, Matteo Mueller, Leslie Cunningham, Michelle L. De Oliveira, Henrik Petrowsky, Achim Weber, Philipp Dutkowski, Waldemar Hoffmann, Anurag Gupta, Mark W. Tibbitt, Bostjan Humar, Pierre-Alain Clavien
Summary: This study developed a protocol for defatting steatotic liver grafts using ex situ normothermic machine perfusion and demonstrated its effectiveness in reducing steatosis and preserving organ viability. This method could potentially increase the pool of usable organs for transplantation.
Review
Medicine, General & Internal
Jeannette Widmer, Janina Eden, Mauricio Flores Carvalho, Philipp Dutkowski, Andrea Schlegel
Summary: The renaissance of dynamic preservation techniques has brought extended criteria donor (ECD) livers back into the transplantable organ pool. However, there is ongoing debate about the advantages and disadvantages of different perfusion strategies and their best applications for specific categories of marginal livers.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Engineering, Biomedical
Charlotte von Horn, Hristo Zlatev, Jessica Pletz, Bastian Lueer, Thomas Minor
Summary: This study investigated the effects of different temperature machine perfusion on reperfusion injury in rat liver grafts. The results showed that near-normothermic recirculation and controlled cooling recirculation groups exhibited lower release of hepatic enzymes and tumor necrosis factor production upon reperfusion, while hypothermic resuscitation had a less protective effect.
Article
Surgery
Cristiano Quintini, Luca Del Prete, Andrea Simioni, Laurent Del Angel, Teresa Diago Uso, Giuseppe D'Amico, Koji Hashimoto, Federico Aucejo, Masato Fujiki, Bijan Eghtesad, Kazunari Sasaki, Choon Hyuck David Kwon, Jacek Cywinski, Ana Bennett, Mary Bilancini, Charles Miller, Qiang Liu
Summary: This study demonstrated the successful transplantation of 71.5% of discarded livers after ex vivo normothermic machine perfusion and assessment using an institutionally built device. The findings challenge the current viability criteria and call for standardization of viability marker collection.
Article
Biotechnology & Applied Microbiology
Pierre-Alain Clavien, Philipp Dutkowski, Matteo Mueller, Dilmurodjon Eshmuminov, Lucia Bautista Borrego, Achim Weber, Beat Muellhaupt, Richard X. Sousa Da Silva, Brian R. Burg, Philipp Rudolf von Rohr, Martin J. Schuler, Dustin Becker, Max Hefti, Mark W. Tibbitt
Summary: A human liver has been successfully transplanted using ex situ normothermic machine perfusion, which extends the time window for evaluating the viability of donor organs and transforms the urgency of the surgery to an elective procedure.
NATURE BIOTECHNOLOGY
(2022)
Article
Immunology
Iris E. M. de Jong, Silke B. Bodewes, Otto B. van Leeuwen, Dorenda Oosterhuis, Veerle A. Lantinga, Adam M. Thorne, Bianca Lascaris, Marius C. van den Heuvel, Rebecca G. Wells, Peter Olinga, Vincent E. de Meijer, Robert J. Porte
Summary: This study found that the chemical composition of bile during NMP is closely related to the viability of the bile ducts, and that the bile ducts of high-risk human donor livers already undergo repair during NMP.
Article
Gastroenterology & Hepatology
Janina Eden, Richard Xavier Sousa Da Silva, Miriam Cortes-Cerisuelo, Kristopher Croome, Riccardo De Carlis, Amelia J. Hessheimer, Xavier Muller, Femke de Goeij, Vanessa Banz, Giulia Magini, Philippe Compagnon, Andreas Elmer, Andrea Lauterio, Rebecca Panconesi, Jeannette Widmer, Daniele Dondossola, Paolo Muiesan, Diethard Monbaliu, Marieke de Rosner van van Rosmalen, Olivier Detry, Constantino Fondevila, Ina Jochmans, Jacques Pirenne, Franz Immer, Gabriel C. Oniscu, Jeroen de Jonge, Mickael Lesurtel, Luciano G. De Carlis, C. Burcin Taner, Nigel Heaton, Andrea Schlegel, Philipp Dutkowski
Summary: Liver graft utilization rates and discard rates vary across countries, with machine perfusion strategies contributing to better DCD utilization rates. Risk factors and use of various machine perfusion techniques vary between countries, but this does not significantly impact 5-year graft survival rates. Overall, countries with routine use of machine perfusion strategies have higher DCD utilization rates without compromised outcomes.
JOURNAL OF HEPATOLOGY
(2023)
Article
Surgery
Matteo Mueller, Max Hefti, Dilmurodjon Eshmuminov, Martin J. Schuler, Richard X. Sousa Da Silva, Henrik Petrowsky, Michelle L. De Oliveira, Christian E. Oberkofler, Catherine Hagedorn, Leandro Mancina, Achim Weber, Brian Burg, Mark W. Tibbitt, Philipp Rudolf von Rohr, Philipp Dutkowski, Dustin Becker, Lucia Bautista Borrego, Pierre-Alain Clavien
Summary: This study successfully achieved the long-term machine perfusion of partial human livers, demonstrating stable perfusion and normal hepatic function and architecture, paving the way for innovative clinical applications and approaches in hepatic oncology.
Article
Immunology
Christopher J. E. Watson, Stephen MacDonald, Christopher Bridgeman, Rebecca Brais, Sara S. Upponi, Theodora Foukaneli, Lisa Swift, Corrina Fear, Linda Selves, Vasilis Kosmoliaptsis, Michael Allison, Rachel Hogg, Kourosh Saeb Parsy, Will Thomas, Rohit Gaurav, Andrew J. Butler
Summary: This study aimed to determine the underlying cause of biliary complications leading to liver retransplantation and evaluate the role of fibrinolysis. The results showed the presence of fibrin during cold storage and its association with poor posttransplant outcomes. Fibrinolytic therapy may be a promising intervention.