Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers

Adam M. Thorne, Justina C. Wolters, Bianca Lascaris, Silke B. Bodewes, Veerle A. Lantinga, Otto B. Leeuwen, Iris E. M. Jong, Kirill Ustyantsev, Eugene Berezikov, Ton Lisman, Folkert Kuipers, Robert J. Porte and Vincent E. Meijer ()
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Adam M. Thorne: University of Groningen and University Medical Center Groningen
Justina C. Wolters: University of Groningen, University of Groningen and University Medical Center Groningen
Bianca Lascaris: University of Groningen and University Medical Center Groningen
Silke B. Bodewes: University of Groningen and University Medical Center Groningen
Veerle A. Lantinga: University of Groningen and University Medical Center Groningen
Otto B. Leeuwen: University of Groningen and University Medical Center Groningen
Iris E. M. Jong: University of Groningen and University Medical Center Groningen
Kirill Ustyantsev: University of Groningen and University Medical Center Groningen
Eugene Berezikov: University of Groningen and University Medical Center Groningen
Ton Lisman: University of Groningen and University Medical Center Groningen
Folkert Kuipers: University of Groningen, University of Groningen and University Medical Center Groningen
Robert J. Porte: University of Groningen and University Medical Center Groningen
Vincent E. Meijer: University of Groningen and University Medical Center Groningen

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Normothermic machine perfusion (NMP) after static cold storage is increasingly used for preservation and assessment of human donor livers prior to transplantation. Biliary viability assessment during NMP reduces the risk of post-transplant biliary complications. However, understanding of molecular changes in the biliary system during NMP remains incomplete. We performed an in-depth, unbiased proteomics analysis of bile collected during sequential hypothermic machine perfusion, rewarming and NMP of 55 human donor livers. Longitudinal analysis during NMP reveals proteins reflective of cellular damage at early stages, followed by upregulation of secretory and immune response processes. Livers with bile chemistry acceptable for transplantation reveal protein patterns implicated in regenerative processes, including cellular proliferation, compared to livers with inadequate bile chemistry. These findings are reinforced by detection of regenerative gene transcripts in liver tissue before machine perfusion. Our comprehensive bile proteomics and liver transcriptomics data sets provide the potential to further evaluate molecular mechanisms during NMP and refine viability assessment criteria.

Date: 2023
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DOI: 10.1038/s41467-023-43368-y

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