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

Author

Listed:
  • Adam M. Thorne

    (University of Groningen and University Medical Center Groningen
    UMCG Comprehensive Transplant Center)

  • Justina C. Wolters

    (University of Groningen, University of Groningen and University Medical Center Groningen)

  • Bianca Lascaris

    (University of Groningen and University Medical Center Groningen
    UMCG Comprehensive Transplant Center)

  • Silke B. Bodewes

    (University of Groningen and University Medical Center Groningen
    UMCG Comprehensive Transplant Center)

  • Veerle A. Lantinga

    (University of Groningen and University Medical Center Groningen
    UMCG Comprehensive Transplant Center)

  • Otto B. Leeuwen

    (University of Groningen and University Medical Center Groningen
    UMCG Comprehensive Transplant Center)

  • Iris E. M. Jong

    (University of Groningen and University Medical Center Groningen
    UMCG Comprehensive Transplant Center)

  • 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
    University of Groningen, University Medical Center Groningen)

  • Folkert Kuipers

    (University of Groningen, University of Groningen and University Medical Center Groningen
    University of Groningen and University Medical Center Groningen)

  • Robert J. Porte

    (University of Groningen and University Medical Center Groningen
    University Medical Center Rotterdam)

  • Vincent E. Meijer

    (University of Groningen and University Medical Center Groningen
    UMCG Comprehensive Transplant Center)

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.

Suggested Citation

  • 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 , 2023. "Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43368-y
    DOI: 10.1038/s41467-023-43368-y
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    References listed on IDEAS

    as
    1. Otto B. van Leeuwen & Yvonne de Vries & Vincent E. de Meijer & Robert J. Porte, 2021. "Hypothermic machine perfusion before viability testing of previously discarded human livers," Nature Communications, Nature, vol. 12(1), pages 1-2, December.
    2. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. David Nasralla & Constantin C. Coussios & Hynek Mergental & M. Zeeshan Akhtar & Andrew J. Butler & Carlo D. L. Ceresa & Virginia Chiocchia & Susan J. Dutton & Juan Carlos García-Valdecasas & Nigel Hea, 2018. "A randomized trial of normothermic preservation in liver transplantation," Nature, Nature, vol. 557(7703), pages 50-56, May.
    4. Hynek Mergental & Richard W. Laing & Amanda J. Kirkham & M. Thamara P. R. Perera & Yuri L. Boteon & Joseph Attard & Darren Barton & Stuart Curbishley & Manpreet Wilkhu & Desley A. H. Neil & Stefan G. , 2020. "Transplantation of discarded livers following viability testing with normothermic machine perfusion," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
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