Liver regeneration investigated in a non-human primate model (Macaca mulatta)

Paul J. Gaglio, Huifeng Liu, Shrikanta Dash, Stephen Cheng, Bruce Dunne, Marion Ratterree, Gary Baskin, James Blanchard, Rudolf Bohm, Neil D. Theise, Douglas LaBrecque

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background/Aims: An adequate model to study liver regeneration in humans is presently unavailable. We explored the feasibility of studying liver regeneration in a genetically similar species to man, the non-human primate Rhesus macaque. Methods: Five animals were studied; two underwent 60% hepatectomy, one underwent 30% hepatectomy, and cholecystectomy alone was performed on two animals. Laparoscopic-guided or open liver biopsies were performed on days 1, 2, 7, 14, 21, 30 and 60 following all surgeries. Liver regeneration was evaluated by measuring Ki-67, proliferating cell nuclear antigen expression and mitotic index, calculating changes in the surface area of the liver remnant and assessing intrahepatic production of cytokines. Results: Significant liver regeneration was induced in the animals that underwent 60% hepatectomy, peaking between days 21-30 postoperatively. Regeneration was minimal in all other animals studied. Cytokine production followed a similar pattern. Maximal liver regeneration correlated with restoration of surface area in the liver remnant. Conclusions: Sixty percent hepatectomy in a non-human primate model induced significant liver regeneration, maximizing 21-30 days following partial hepatectomy, suggesting a significant interspecies difference when compared to a rodent hepatectomy model. A partial hepatectomy model in Rhesus macaques may allow further characterization of liver regeneration in a species closer to humans.

Original languageEnglish (US)
Pages (from-to)625-632
Number of pages8
JournalJournal of Hepatology
Volume37
Issue number5
DOIs
StatePublished - Nov 1 2002

Keywords

  • Ki-67
  • Liver regeneration
  • Partial hepatectomy

ASJC Scopus subject areas

  • Hepatology

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