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Transcriptomic signatures during normothermic liver machine perfusion correspond with graft quality and predict the early graft function.
Hautz, Theresa; Hackl, Hubert; Gottschling, Hendrik; Gronauer, Raphael; Hofmann, Julia; Salcher, Stefan; Zelger, Bettina; Oberhuber, Rupert; Cardini, Benno; Weissenbacher, Annemarie; Resch, Thomas; Troppmair, Jakob; Schneeberger, Stefan.
Afiliación
  • Hautz T; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria. Electronic address: Theresa.hautz@i-med.
  • Hackl H; Institute of Bioinformatics, Biocentre, Medical University of Innsbruck, Innrain 80/82, A-6020, Innsbruck, Austria.
  • Gottschling H; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Gronauer R; Institute of Bioinformatics, Biocentre, Medical University of Innsbruck, Innrain 80/82, A-6020, Innsbruck, Austria.
  • Hofmann J; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Salcher S; Department of Internal Medicine V, Haematology and Oncology, Comprehensive Cancer Centre Innsbruck (CCCI), Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Zelger B; Institute of Pathology, Medical University of Innsbruck, Muellerstr. 44, A-6020, Innsbruck, Austria.
  • Oberhuber R; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Cardini B; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Weissenbacher A; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Resch T; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Troppmair J; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
  • Schneeberger S; OrganLife Organ Regeneration Centre of Excellence and Daniel Swarovski Research Laboratory (DSL), Department of Visceral, Transplant and Thoracic Surgery, Centre of Operative Medicine, Medical University of Innsbruck, Anichstr. 35, A-6020, Innsbruck, Austria.
EBioMedicine ; 108: 105330, 2024 Sep 18.
Article en En | MEDLINE | ID: mdl-39299005
ABSTRACT

BACKGROUND:

A better understanding of the molecular events during liver normothermic machine perfusion (NMP) is warranted to develop a data-based approach for the identification of biomarkers representative of graft quality and posttransplant outcome. We analysed the dynamic transcriptional changes during NMP and linked them to clinical and biochemical parameters.

METHODS:

50 livers subjected to NMP for up to 24 h were enrolled. Bulk RNA sequencing was performed in serial biopsies collected pre and during NMP, and after reperfusion. Perfusate was sampled to monitor liver function. qPCR and immunohistochemistry were performed to validate findings. Molecular profiles were compared between transplanted and non-transplanted livers, and livers with and without early allograft dysfunction.

FINDINGS:

Pathways related to immune and cell stress responses, cell trafficking and cell regulation were activated during NMP, while cellular metabolism was downregulated over time. Anti-inflammatory responses and genes involved in tissue remodelling were induced at later time-points, suggesting a counter-response to the immediate damage. NMP strongly induced a gene signature associated with ischemia-reperfusion injury. A 7-gene signature corresponds with the benchmarking criteria for transplantation or discard at 6 h NMP (area under curve 0.99). CD274 gene expression (encoding programmed cell-death ligand-1) showed the highest predictive value. LEAP2 gene expression at 6 h NMP correlated with impaired graft function.

INTERPRETATION:

Assessment of gene expression markers could serve as a reliable tool to evaluate liver quality during NMP and predicts early graft function after transplantation.

FUNDING:

The research was supported by "In Memoriam Dr. Gabriel Salzner Stiftung", Tiroler Wissenschaftsfond, Jubiläumsfonds-Österreichische Nationalbank and MUI Start grant.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EBioMedicine Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: EBioMedicine Año: 2024 Tipo del documento: Article Pais de publicación: Países Bajos