Background: Previous studies have shown better liver regeneration and improved survival after partial hepatectomy in granulocyte colony stimulating factor (G-CSF)-conditioned animals. Little is known about the molecular and biochemical mechanisms involved in this G-CSF effect. The aim of the presented study was to determine the impact of systemically administered (G-CSF) on the hepatic microvasculature during liver regeneration after partial hepatectomy.
Methods: Male Balb/c mice were conditioned daily for 5 days with either 5μg G-CSF or normal saline. A 60% partial hepatectomy was then performed and daily injections of G-CSF or aqua ad injectabile continued. Three groups of animals were examined by intravital microscopy: (i) Control animals at day 0 before liver resection, (ii) Sham-conditioned and resected animals, and (iii) G-CSF-conditioned and resected animals at 48 hours postoperatively. After analyses, animals were sacrificed and the remnant liver lobes and the spleen excised. Dry and moist weights were determined and samples were taken for immunohistological examination.
Results: Moist and dry spleen weight was significantly higher in G-CSF-treated animals compared to sham and control animals. No significant differences were found in moist and dry remnant liver weights between the resected groups. In intravital microscopy the sinusoidal diameter was higher in G-CSF-treated animals (p<0.05 vs control, p<0.05 vs sham). Hepatic cell plate width was enlarged in the G-CSF-treatment group (p<0.05 vs sham). No differences in the sinusoidal blood velocity were found between the experimental groups. Sinusoidal blood flow was lowest in control animals and significantly higher in sham (p<0.05 vs control), and highest in G-CSF treated mice (p<0.05 vs control, p<0.05 vs sham). Immunohistochemistry at 48 hours after partial hepatectomy showed elevated proliferation indexes in G-CSF pretreated animals compared to sham controls (p < 0.05).
Conclusions: The presented results reveal significant and surprising group-specific alterations in the hepatic and vascular microanatomy of the regenerating liver. Consequently differences in the in vivo perfusion pattern between the three examined experimental groups were also detected. The cellular and molecular mechanisms involved in the described unexpected G-CSF properties merit further investigation.