Normothermic Ex Vivo Liver Platform Using Porcine Slaughterhouse Livers for Disease Modeling

Autor: Krüger, Melanie, Ruppelt, Alicia, Kappler, Benjamin, Van Soest, Elke, Samsom, Roos Anne, Grinwis, Guy C M, Geijsen, Niels, Helms, J Bernd, Stijnen, Marco, Kock, Linda M, Rasponi, Marco, Kooistra, Hans S, Spee, Bart, Interne geneeskunde GD, VPDC pathologie, dPB CR, VP pathologie, Veterinaire biochemie, CS_Welfare & emerging diseases, CS_STEM
Přispěvatelé: Interne geneeskunde GD, VPDC pathologie, dPB CR, VP pathologie, Veterinaire biochemie, CS_Welfare & emerging diseases, CS_STEM, Cardiovascular Biomechanics, Orthopaedic Biomechanics
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Bioengineering
Bioengineering, 9(9):471. Multidisciplinary Digital Publishing Institute (MDPI)
Bioengineering; Volume 9; Issue 9; Pages: 471
Bioengineering (Basel, Switzerland), 9(9), 1. MDPI AG
ISSN: 2306-5354
Popis: Metabolic and toxic liver disorders, such as fatty liver disease (steatosis) and drug-induced liver injury, are highly prevalent and potentially life-threatening. To allow for the study of these disorders from the early stages onward, without using experimental animals, we collected porcine livers in a slaughterhouse and perfused these livers normothermically. With our simplified protocol, the perfused slaughterhouse livers remained viable and functional over five hours of perfusion, as shown by hemodynamics, bile production, indocyanine green clearance, ammonia metabolism, gene expression and histology. As a proof-of-concept to study liver disorders, we show that an infusion of free fatty acids and acetaminophen results in early biochemical signs of liver damage, including reduced functionality. In conclusion, the present platform offers an accessible system to perform research in a functional, relevant large animal model while avoiding using experimental animals. With further improvements to the model, prolonged exposure could make this model a versatile tool for studying liver diseases and potential treatments.
Databáze: OpenAIRE