Liver regeneration investigated in a non-human primate model (Macaca mulatta).
OBJECTIVE
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.
Gaglio
Paul J
PJ
Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA. pg2011@columbia.edu
Liu
Huifeng
H
Dash
Shrikanta
S
Cheng
Stephen
S
Dunne
Bruce
B
Ratterree
Marion
M
Baskin
Gary
G
Blanchard
James
J
Bohm
Rudolf
R
Theise
Neil D
ND
LaBrecque
Douglas
D
D000818:Animals; D015139:Blotting, Southern; D002455:Cell Division / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D019394:Ki-67 Antigen / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D008115:Liver Regeneration / Q000502:physiology*; D008253:Macaca mulatta; D008297:Male; D008938:Mitosis / Q000502:physiology; D023421:Models, Animal; D010865:Pilot Projects; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016211:Transforming Growth Factor alpha / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015850:Interleukin-6; D019394:Ki-67 Antigen; D018809:Proliferating Cell Nuclear Antigen; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D017228:Hepatocyte Growth Factor