Normothermic machine perfusion converges transplant induced transcript profiles in low and high risk DBD and DCD livers
Normothermic machine perfusion (NMP) of donated livers is emerging as a superior preservation technology versus static cold storage (SCS) for transplant, transforming a metabolically dormant organ to a functioning state that improves outcomes of marginal liver transplants. Mechanisms underlying improved NMP restoration of donation after brain death (DBD) and donation after circulatory death (DCD) livers remain incompletely defined. We tested the hypothesis that NMP would decrease transcripts encoding inflammatory mediators following both perfusion and transplant of DBD and DCD livers. Biopsy transcript expression profiles were determined from SCS DBD livers at pre-SCS preservation and transplant reperfusion and from benchmark and outside benchmark criteria DBD and DCD livers pre-NMP, after 6-7 h of NMP, and after transplant reperfusion. Compared to SCS livers, NMP programs converged transcript profiles of DCD and DBD livers, decreasing transplant reperfusion-induced inflammatory transcripts while increasing transcripts promoting wound healing and tissue repair processes, but did not obviate the high occurrence of adverse events in the outside benchmark DCD livers transplants.
Authors
- Luca Del Prete (ORCID: https://orcid.org/0000-0003-0268-3266)
- Mingyi Zhang (ORCID: https://orcid.org/0009-0006-6080-0036)
- Beatrice Cazzaniga (ORCID: https://orcid.org/0000-0002-3180-9078)
- Chunbao Jiao (ORCID: https://orcid.org/0000-0002-9566-8243)
- Khaled Ali (ORCID: https://orcid.org/0000-0002-9114-897X)
- Cristiano Quintini (ORCID: https://orcid.org/0000-0002-6802-1436)
- William M. Baldwin (ORCID: https://orcid.org/0000-0002-7271-1827)
- Keyue Sun (ORCID: https://orcid.org/0000-0002-8928-4630)
- Brian T. Gaudette (ORCID: https://orcid.org/0000-0001-6627-3085)
- Koji Hashimoto (ORCID: https://orcid.org/0000-0002-2327-6777)
- Chase J. Wehrle (ORCID: https://orcid.org/0000-0002-9275-4744)
- Andrea Schlegel (ORCID: https://orcid.org/0000-0002-9385-9847)
- Robert L. Fairchild (ORCID: https://orcid.org/0000-0002-7107-5259)
- Charles M. Miller (ORCID: https://orcid.org/0000-0001-6413-7389)
- Karen S. Keslar (ORCID: https://orcid.org/0000-0001-8609-4797)
- Qiang Liu (ORCID: https://orcid.org/0000-0001-8126-9295)
Institutions
- Cleveland Clinic (US)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Cleveland Clinic Lerner College of Medicine (US)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-10-02
- DOI
- https://doi.org/10.1038/s41598-025-17448-6
- Citations
- 1
- Primary Topic
- Organ Transplantation Techniques and Outcomes
- Type
- article
- Field-Weighted Citation Impact
- 2.01
Funders
- Cleveland Clinic
- National Institute of Allergy and Infectious Diseases