TY - JOUR
T1 - Liver regeneration investigated in a non-human primate model (Macaca mulatta)
AU - Gaglio, Paul J.
AU - Liu, Huifeng
AU - Dash, Shrikanta
AU - Cheng, Stephen
AU - Dunne, Bruce
AU - Ratterree, Marion
AU - Baskin, Gary
AU - Blanchard, James
AU - Bohm, Rudolf
AU - Theise, Neil D.
AU - LaBrecque, Douglas
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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.
AB - 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.
KW - Ki-67
KW - Liver regeneration
KW - Partial hepatectomy
UR - http://www.scopus.com/inward/record.url?scp=0036845763&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036845763&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(02)00262-3
DO - 10.1016/S0168-8278(02)00262-3
M3 - Article
C2 - 12399229
AN - SCOPUS:0036845763
SN - 0168-8278
VL - 37
SP - 625
EP - 632
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 5
ER -