Transcriptomic profiles of human livers undergoing rewarming machine perfusion before transplantation-first insights.

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.