Granulocyte colony-stimulating factor supports liver regeneration in a small-for-size liver remnant mouse model.
Experimental partial hepatectomy of more than 80% of the liver weight bears an increased mortality in rodents, due to impaired hepatic regeneration in small-for-size liver remnants. Granulocyte colony-stimulating factor (G-CSF) promotes progenitor cell expansion and mobilization and also has immunomodulatory properties. The aim of this study was to determine the effect of systemically administered G-CSF on liver regeneration and animal survival in a small-for-size liver remnant mouse model. Mice were preconditioned daily for 5 days with subcutaneous injections of 5 microg G-CSF or aqua ad injectabile. Subsequently, 83% partial hepatectomy was performed by resecting the median, the left, the caudate, and the right inferior hepatic lobes in all animals. Daily sham or G-CSF injection was continued. Survival was significantly better in G-CSF-treated animals (P < 0.0001). At 36 and 48 h after microsurgical hepatic resection, markers of hepatic proliferation (Ki67, BrdU) were elevated in G-CSF-treated mice compared to sham injected control animals (P < 0.0001) and dry liver weight was increased (P < 0.05). G-CSF conditioning might prove to be useful in patients with small-for-size liver remnants after extended hepatic resections due to primary or secondary liver tumors or in the setting of split liver transplantation.
Inderbitzin
Daniel
D
Department of Visceral and Transplantation Surgery, University Hospital Bern, 3010, Bern, Switzerland. daniel.inderbitzin@insel.ch
Beldi
Guido
G
Sidler
Daniel
D
Studer
Peter
P
Keogh
Adrian
A
Bisch-Knaden
Sonja
S
Weimann
Rosy
R
Kappeler
Andreas
A
Gloor
Beat
B
Candinas
Daniel
D
D000818:Animals; D001973:Bromodeoxyuridine; D049109:Cell Proliferation / Q000187:drug effects; D004396:Coloring Agents; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006498:Hepatectomy; D017730:Ki-1 Antigen / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size
D004396:Coloring Agents; D017730:Ki-1 Antigen; D016179:Granulocyte Colony-Stimulating Factor; D001973:Bromodeoxyuridine