title: Granulocyte colony-stimulating factor increases hepatic sinusoidal perfusion during liver regeneration in mice.
abstract: Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver regeneration in an experimental small-for-size liver remnant mouse model. The mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of this study was to investigate the influence of G-CSF on the hepatic microvasculature in the regenerating liver. The hepatic sinusoidal microvasculature and microarchitecture of the regenerating liver were evaluated by intravital microscopy in mice. Three experimental groups were compared: (1) unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G-CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups. Increased sinusoidal diameter and increased hepatic blood flow were observed in the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there was a strong positive correlation between spleen weight and hepatic sinusoidal diameter in the G-CSF-PH group. The increased hepatic blood flow could explain the observed benefit of G-CSF conditioning during liver regeneration. These results elucidate an unexplored aspect of pharmacological modulation of liver regeneration and motivate further experiments.
authors.affiliation: Department of Visceral and Transplant Surgery, University Hospital Bern, Bern, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sidler
authors.forename: Peter
authors.initials: P
authors.lastname: Studer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Küpper
authors.forename: Beat
authors.initials: B
authors.lastname: Gloor
authors.forename: Daniel
authors.initials: D
authors.lastname: Candinas
authors.forename: Jörg
authors.initials: J
authors.lastname: Haier
authors.forename: Daniel
authors.initials: D
authors.lastname: Inderbitzin
mesh_terms: D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006498:Hepatectomy; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism / Q000601:surgery; D008102:Liver Circulation / Q000187:drug effects*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation; D009929:Organ Size
chemical_list: D019394:Ki-67 Antigen; D016179:Granulocyte Colony-Stimulating Factor