Dataset Information

Proteomic profiling during normothermic perfusion predicts liver graft quality and outcomes after transplantation

ABSTRACT: This study investigates the proteomic dynamics of human liver grafts during normothermic machine perfusion (NMP), using mass spectrometry-based analysis. A total of 16 donor livers were perfused with NMP and sampled at three distinct time points to assess molecular changes and their association with post-transplant outcomes. The aim was to identify proteomic biomarkers predictive of graft quality and biliary complications.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver

SUBMITTER: Dupuy Jean-William

LAB HEAD: Heithem Jeddou

PROVIDER: PXD067270 | Pride | 2026-04-27

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

Items per page:

1 - 5 of 147

Publications

Proteomic Trajectories of Metabolic and Proteostatic Adaptation During Normothermic Liver Perfusion.

Jeddou Heithem H Raymond Anne-Aurélie AA Dupuy Jean-William JW Dourthe Cyril C Prudhomme Hector H Nejma Eya Ben EB Tzedakis Stylianos S Turlin Bruno B Allaume Pierre P Boudjema Karim K Samson Michel M

Liver international : official journal of the International Association for the Study of the Liver 20260501 5

<h4>Background</h4>Normothermic machine perfusion (NMP) enables metabolic restoration and viability testing of liver grafts, but current viability criteria incompletely predict post-transplant outcomes. The molecular basis of graft resilience or biliary vulnerability remains unclear. This study aimed to characterise tissue-level proteomic trajectories during NMP and early reperfusion to identify molecular signatures associated with biliary complications after liver transplantation (LT).<h4>Metho ...[more]

PMID: 41981940

Similar Datasets

Project description:Assessment and treatment of severe ischaemia-reperfusion-injury (IRI) remains an unmet challenge in kidney transplantation. Normothermic machine perfusion (NMP) recapitulates IRI ex situ, but there is limited understanding of the transcriptional pathways, and the associated cellular landscape, driving IRI during NMP and determining its severity. Such knowledge is essential for therapeutic targeting and organ resuscitation during machine perfusion. Using tissue obtained at the time of NMP from kidneys subsequently transplanted as part of a randomised controlled trial, we undertook in-depth transcriptomic analyses comparing kidneys suffering severe IRI, manifesting clinically as the development of delayed graft function (DGF), to kidneys with mild IRI (defined by immediate graft function, IGF) post-transplantation. We validated upregulation of previously described pro-inflammatory and immune transcriptomic pathways, including TNFa via NFkB signaling, Allograft Rejection and Inflammatory Response. Going further, we identified innate immune system driven processes at the core of the transcriptional signature in kidneys suffering severe IRI, such as recruitment and migration of myeloid leucocytes, macrophage activation, phagocytosis and inflammasome activation. Deconvolution using single-cell-RNAseq data showed kidneys with severe IRI and post-transplant DGF were enriched for pro-inflammatory mononuclear phagocytes, myofibroblasts and fibroblasts, but depleted of tubuloepithelial, cell signatures. These transcriptional findings were recapitulated in tissue biopsies obtained during NMP from an external cohort comparing kidneys with high acute tubular injury and severe IRI to kidneys with low acute tubular injury and mild IRI; these kidneys were histologically similar to the DGF/IGF kidneys, respectively. Together, our study characterises the transcriptional signature of severe IRI during NMP, suggesting the role of pro-inflammatory innate/pro-fibrotic cells in this process. We describe a transcriptomic signature that may support future prospective therapeutic trials as a potential efficacy endpoint, and highlight potential cellular targets for therapeutic intervention during NMP in an era of precision medicine.

			Action	DRS
	Link_between_files.xlsx	Xlsx
	RP_UP000005640_Homo_sapiens_2025_01_23.fasta	Fasta
	checksum.txt	Txt
	jh250422_01b.msf	Msf
	jh250422_01b.pdResult	Other