Abstract
Machine perfusion by controlled oxygenated rewarming (COR) is feasible and safe in clinical application and result in a promising outcome. This study utilizes next-generation sequencing (NGS) to investigate the transcriptome of human liver tissue undergoing COR before liver transplantation. Cold-stored livers were subjected to machine-assisted slow COR for ~120 min before transplantation. Biopsies were taken before (preCOR) and after COR (postCOR) and 1 h after reperfusion (postRep). The samples were sequenced, using RNA-seq to analyze differential transcriptional changes between the different stages and treatments of the grafts. Comparison of differential gene expression preCOR and postCOR demonstrated 10 upregulated genes. postRep 97 and 178 genes were upregulated and 7 and 13 downregulated compared to preCOR and postCOR, respectively. A shift of gene expressions by machine perfusion to the TGF-beta pathway was observed. The present study demonstrates distinct transcriptome profiles associated with machine perfusion by COR and transplantation of human livers. Such data provide a deeper understanding of the molecular mechanisms of machine perfusion technology in human liver transplantation.
Highlights
Key elements in liver transplantation are allograft procurement, preservation, and reperfusion in the recipient
Extensive research analyzed mechanisms whereby this cascade of anoxia and reoxygenation leads to injury of the allograft
This so-called ischemia-reperfusion injury results in parenchymal cell death, microcirculatory failure, and inflammatory immune responses. The intensity of this injury is clinically observed by the development of good graft function, early allograft dysfunction, or even primary non-function
Summary
Key elements in liver transplantation are allograft procurement, preservation, and reperfusion in the recipient. Extensive research analyzed mechanisms whereby this cascade of anoxia and reoxygenation leads to injury of the allograft. This so-called ischemia-reperfusion injury results in parenchymal cell death, microcirculatory failure, and inflammatory immune responses. The intensity of this injury is clinically observed by the development of good graft function, early allograft dysfunction, or even primary non-function. With translation from preclinical models into clinical studies, was shown for the application of different perfusion technologies (Hoyer et al 2016a; Guarrera et al 2015; Minor et al 2013; Fondevila et al 2012; Hoyer et al 2016b). We described in a series of preclinical and clinical studies the protective effect of incremental temperature management during machine
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