Granulocyte colony-stimulating factor enhances bone marrow mononuclear cell homing to the liver in a mouse model of acute hepatic injury

Dig Dis Sci. 2010 Oct;55(10):2805-13. doi: 10.1007/s10620-009-1117-5. Epub 2010 Feb 4.

Abstract

Background: Experiments have reported that granulocyte colony stimulating factor (G-CSF) can mobilize stem cells. However, few studies have examined the effect of G-CSF on bone marrow mononuclear cell (BMMC) mobilization, in particular regarding their capability to home to acutely injured liver.

Aims: The aim of this study was to evaluate the effort of G-CSF on BMMC homing to the liver following chemically-induced hepatic failure.

Methods: BMMC were isolated from mice, pre-labeled with PKH26 and infused into the mice in which hepatic injury had been induced followed by administration of G-CSF or vehicle. Livers were studied by fluorescent microscopy after transplantation of pre-labeled BMMC.

Results: PKH26 labeled cells were found in liver tissue at 102 ± 10 cells/high power field in the BMMC+G-CSF group and 30 ± 5 cells/high power field in the BMMC group, but none in the G-CSF group and the control group (P < 0.05). In the former two groups the majority of PKH26 labeled cells colocalized with proliferative cell nuclear antigen (PCNA). The number of PCNA positive cells in the BMMC+G-CSF group was 20 ± 4 cells/high power field, while in the BMMC group it was 14 ± 2 cells/high power field, in the G-CSF group 12 ± 2 cells/high power field, and 8 ± 1 cells/high power field in the control group. Moreover, albumin expression was increased in the BMMC+G-CSF treated group (149 ± 7/high power field) relative to the BMMC group (48 ± 6/high power field), the G-CSF group (44 ± 5/high power field) and the vehicle group (30 ± 6/high power field), with the former three groups showing elevated levels as compared to vehicle control (30 ± 6) (P < 0.05).

Conclusion: Transplanted BMMC may home to injured liver, which appears to be enhanced by G-CSF administration.

MeSH terms

  • Albumins / metabolism
  • Animals
  • Biopsy
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Transplantation*
  • Carbon Tetrachloride / toxicity
  • Cell Movement / drug effects
  • Cells
  • Disease Models, Animal
  • Flow Cytometry
  • Fluorescent Dyes
  • Granulocyte Colony-Stimulating Factor / pharmacology*
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Immunohistochemistry
  • Liver / cytology
  • Liver Failure, Acute / chemically induced
  • Liver Failure, Acute / drug therapy*
  • Liver Failure, Acute / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organic Chemicals

Substances

  • Albumins
  • Fluorescent Dyes
  • Organic Chemicals
  • PKH 26
  • Granulocyte Colony-Stimulating Factor
  • Carbon Tetrachloride