Details

Autor(en) / Beteiligte

• Thorne, Adam M.
• Wolters, Justina C.
• Lascaris, Bianca
• Bodewes, Silke B.
• Lantinga, Veerle A.
• van Leeuwen, Otto B.
• de Jong, Iris E. M.
• Ustyantsev, Kirill
• Berezikov, Eugene
• Lisman, Ton
• Kuipers, Folkert
• Porte, Robert J.
• de Meijer, Vincent E.

Titel

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

Ist Teil von

• Nature communications, 2023-11, Vol.14 (1), p.7880-7880, Article 7880

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2023

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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.