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

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 i...

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Published inBioengineering (Basel) Vol. 9; no. 9; p. 471
Main Authors 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
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.09.2022
MDPI
Subjects
Abattoirs
Acetaminophen
Ammonia
Analgesics
Animal models
Animals
Anticoagulants
Bioengineering
Disorders
Fatty acids
Fatty liver
Food
Gene expression
Hemodynamics
hepatic diseases
Histology
Hogs
Liver
Liver diseases
machine perfusion
Nonsteroidal anti-inflammatory drugs
Physiological aspects
Steatosis
Toxic diseases
Transplants & implants
Netherlands
Ireland
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Summary: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.
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These authors contributed equally to this work.
ISSN:2306-5354
2306-5354
DOI:10.3390/bioengineering9090471