Bioengineering (Sep 2022)

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

  • Melanie Krüger,
  • Alicia Ruppelt,
  • Benjamin Kappler,
  • Elke Van Soest,
  • Roos Anne Samsom,
  • Guy C. M. Grinwis,
  • Niels Geijsen,
  • J. Bernd Helms,
  • Marco Stijnen,
  • Linda M. Kock,
  • Marco Rasponi,
  • Hans S. Kooistra,
  • Bart Spee

DOI
https://doi.org/10.3390/bioengineering9090471
Journal volume & issue
Vol. 9, no. 9
p. 471

Abstract

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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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