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Granulocyte Colony-stimulating Factor Supports Liver Regeneration in a Small-for-size Liver Remnant Mouse Model
Authors:Daniel Inderbitzin  Guido Beldi  Daniel Sidler  Peter Studer  Adrian Keogh  Sonja Bisch-Knaden  Rosy Weimann  Andreas Kappeler  Beat Gloor  Daniel Candinas
Affiliation:(1) Department of Visceral and Transplantation Surgery, University Hospital Bern, 3010 Bern, Switzerland;(2) Department of Pathology, University Hospital Bern, 3010 Bern, Switzerland
Abstract: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 μg 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. Presented at the Forty-seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, CA, May 14–19, 2006 (poster presentation).
Keywords:Liver regeneration  Granulocyte colony-stimulating factor   In vivo study  Rodent
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