Feasibility and safety of G-CSF administration to induce bone marrow-derived cells mobilization in patients with end stage liver disease.
OBJECTIVE
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.
Gaia
Silvia
S
Gastroenterology, San Giovanni Battista Hospital 10126 Turin, Italy. silvia.gaia@fastwebnet.it
Smedile
Antonina
A
Omedè
Paola
P
Olivero
Antonella
A
Sanavio
Fiorella
F
Balzola
Federico
F
Ottobrelli
Antonio
A
Abate
Maria Lorena
ML
Marzano
Alfredo
A
Rizzetto
Mario
M
Tarella
Corrado
C
D000368:Aged; D015703:Antigens, CD / Q000097:blood; D018952:Antigens, CD34 / Q000097:blood; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003114:Colony-Forming Units Assay; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use* / Q000633:toxicity; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006501:Hepatic Encephalopathy / Q000628:therapy*; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D013154:Spleen / Q000473:pathology; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D016896:Treatment Outcome
D015703:Antigens, CD; D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor