Normothemic Machine Perfusion of Liver Grafts Promotes Liver Regeneration and Inhibits Tissue Inflammation
Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, United Kingdom
Plataforma de Bioinformatica, Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clinic, Centre Esther Koplovitz (CEK), Barcelona, Spain
Nuffield Department of Surgical Sciences, Oxford University, Oxford, United Kingdom.
Meeting: 2015 American Transplant Congress
Abstract number: 509
Keywords: Gene expression, Liver transplantation
Session Information
Session Name: Concurrent Session: Strategies To Minimize Ischemia Reperfusion Injury
Session Type: Concurrent Session
Date: Tuesday, May 5, 2015
Session Time: 4:00pm-5:30pm
Presentation Time: 5:12pm-5:24pm
Location: Room 119-B
Background & aim: liver transplantation I/R injury is associated with inflammation, affecting graft outcome. Ex-vivo normothermic machine perfusion (NMP) to donor livers before transplantation reduces I/R injury, improves the function of transplanted livers and permits the use of more allografts. We aimed to assess the impact of NMP by defining the gene expression profiling of liver tissue and compared to cold storage (CS).
Methods: Liver biopsies were performed pre- and 2 hours post-perfusion for both NMP and CS conditions. Liver tissues were collected from 9 grafts donated after brain death (DBD) and 2 after cardiac death (DCD) and compared to 11 CS grafts, 9 DBD and 2 DCD grafts. Gene expression was assessed using Illumina WG-ADSL array, the level of gene expression was evaluated by gene set enrichment analysis. The expression pattern of 7 genes was quantified using real-time PCR experiments.
Results: comparing gene expression between pre- and post-reperfusion biopsies, 398 genes in NMP and 382 in CS showed significant increased expression. Among these genes, 153 were common in both conditions. Decreased gene expression was seen in 276 genes in NMP grafts and 160 CS grafts, only 36 genes were in common. Genes upregulated after NMP were mainly those involved in tissue regeneration, tissue growth/repair and those involved in control of inflammation. In contrast, upregulated genes in CS were mainly those implicated in inflammation, apotosis and activation of coagulation. Expression pattern of a set of 7 genes was defined by qPCR: IRF1, IL-1 and ICAM-1 post-perfusion were lower in NMP grafts versus CS grafts. There was no difference in gene expression level for IL-10, IFNγ, SOCS1 and TGF-beta.
Conclusion: 1) The gene expression pattern is significantly different between NMP and CS liver grafts; 2) at an early stage post-perfusion, NMP promotes tissue repairing/generation and controls inflammation process; 3) long term benefit of NMP should be defined in future investigation.
To cite this abstract in AMA style:
Xystrakis E, Lozano J, Danger R, Martinez-Llordella M, Srinivasan P, Heaton N, Coussios C, Sanchez-Fueyo A, Ma Y, Jassem W. Normothemic Machine Perfusion of Liver Grafts Promotes Liver Regeneration and Inhibits Tissue Inflammation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/normothemic-machine-perfusion-of-liver-grafts-promotes-liver-regeneration-and-inhibits-tissue-inflammation/. Accessed May 31, 2025.« Back to 2015 American Transplant Congress