Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease

J Hepatol. 2006 Jul;45(1):13-9. doi: 10.1016/j.jhep.2006.02.018. Epub 2006 Apr 6.

Abstract

Background/aims: To evaluate feasibility, safety and pattern of bone marrow-derived cells (BMC) mobilization in patients with end stage liver cirrhosis following granulocyte-colony stimulating factor (G-CSF) administration.

Methods: Eight patients with severe liver cirrhosis (Child-Pugh score B-C, spleen diameter less than 170 mm) were included. They were treated with G-CSF (5 microg/kg b.i.d for three consecutive days) to mobilize BMC, evaluated as circulating CD34+ve cells (flow cytometry) and myeloid CFU-GM progenitors (in vitro colony growth assay). Co-expression in CD34+ve cells markers of differentiation (Thy1, CD133, CXCR4, c1qRp) were investigated on CD34+ve cells by double direct immunofluorescence. Data from 40 healthy haematopoietic stem cell donors were used as controls.

Results: Mobilization of CD34+ve cells occurred in all patients. It was paralleled by expansion of circulating CFU-GM progenitors. Circulating CD34+ve cells co-expressed epithelial and stem cell markers in both cirrhotics and volunteer stem cell donors. G-CSF was well tolerated, no adverse event occurred, a significant reversible increase of splenic longitudinal diameter was observed.

Conclusions: (i) G-CSF mobilization of BMC co-expressing epithelial and stem markers occurred in all cirrhotic patients; (ii) splenomegaly up to 170 mm does not prevent safe BMC mobilization following G-CSF in patients with end stage liver disease; (iii) mobilized BMC may represent an easy immature cell source potentially useful for novel approaches for liver regeneration.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD / blood
  • Antigens, CD34 / blood
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / physiology*
  • Colony-Forming Units Assay
  • Female
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Granulocyte Colony-Stimulating Factor / toxicity
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hepatic Encephalopathy / therapy*
  • Humans
  • Leukocyte Count
  • Male
  • Middle Aged
  • Recombinant Proteins
  • Spleen / pathology
  • Stem Cell Transplantation / adverse effects
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Treatment Outcome

Substances

  • Antigens, CD
  • Antigens, CD34
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor