Normothermic Machine Perfusion of Explanted Human Metabolic Livers: A Proof of Concept for Studying Inborn Errors of Metabolism
The human liver plays a central metabolic role; however, its physiology may become imbalanced in inborn errors of metabolism (IEM), a broad category of monogenic disorders. Liver transplantation has been increasingly used to improve patient metabolic control, especially in diseases related to amino acid metabolism, such as urea cycle disorders and organic acidurias, to provide enzyme replacement. Ex vivo liver normothermic machine perfusion (NMP) techniques have recently been developed to increase the number of transplantable grafts and improve transplantation outcomes. This study used seven NMP of explanted livers from patients with IEM undergoing transplantation as models to investigate disease-related liver metabolism and function. The perfused livers demonstrated positive viability indicators and disease-specific targeted metabolomics providing the proof-of-principle that our ex vivo model expresses the biochemical disease characteristics and responds to therapeutical intervention in a unique "physiological" milieu, offering an ideal tool to study novel treatments, in a setting closely mirroring human disease.
Authors
- Giulia Bravetti (ORCID: https://orcid.org/0009-0002-5218-3593)
- Alberto Maria Fratti
- Marco Spada (ORCID: https://orcid.org/0000-0003-0796-6847)
- Andrea Pietrobattista (ORCID: https://orcid.org/0000-0002-4426-0395)
- Sara Cairoli (ORCID: https://orcid.org/0000-0002-5925-0974)
- Giovina Di Felice (ORCID: https://orcid.org/0000-0003-2610-6842)
- Christian Albano
- Michèle Vacca (ORCID: https://orcid.org/0000-0002-1973-224X)
- Rosanna Pariante (ORCID: https://orcid.org/0000-0003-4370-7439)
- Gionata Spagnoletti (ORCID: https://orcid.org/0000-0003-2626-8147)
- Andrea Cappoli (ORCID: https://orcid.org/0000-0003-0675-2708)
- Raffaele Simeoli (ORCID: https://orcid.org/0000-0002-3989-7703)
- Elisa Sacchetti (ORCID: https://orcid.org/0000-0002-0056-9702)
- Samira Safarikia (ORCID: https://orcid.org/0000-0002-7254-0634)
- Annamaria D’Alessandro
- Cristiano Rizzo (ORCID: https://orcid.org/0000-0002-5954-9749)
- Rosemary Cirelli
- Diego Martinelli (ORCID: https://orcid.org/0000-0002-9324-2871)
- Carlo Dionisi‐Vici (ORCID: https://orcid.org/0000-0002-0007-3379)
- Paola Francalanci
- Elena Baldissone
- Marta Maistri
Institutions
- Bambino Gesù Children's Hospital (IT)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
Publication Details
- Journal
- Journal of Inherited Metabolic Disease
- Published
- 2025-03-01
- DOI
- https://doi.org/10.1002/jimd.70010
- Citations
- 2
- Primary Topic
- Organ Transplantation Techniques and Outcomes
- Type
- article
- Field-Weighted Citation Impact
- 4.01
Funders
- Ministero della Salute