Stem cell mobilization and collection in patients with liver cirrhosis.
BACKGROUND
Bone marrow-derived stem cells (BMSC) and granulocyte colony-stimulating factor (G-CSF) have been proved to contribute to tissue regeneration after liver injury.


OBJECTIVE
To test the safety of G-CSF and define the exact dose capable of mobilizing BMSC in the majority of patients with liver cirrhosis; and to assess the feasibility of leukapheresis to collect BMSC from peripheral blood.


METHODS
In this study, we treated 18 patients affected by liver cirrhosis with increasing doses of G-CSF to mobilize CD34(+) and CD133(+) BMSC into the peripheral blood.


RESULTS
The dose-finding phase demonstrated that 15 microg/kg/day of G-CSF is the optimal dose to mobilize both CD34(+) and CD133(+) stem cells. Circulating BMSC were collected by a single step leukapheresis in three patients and the mean number of CD34(+) and CD133(+) cells cryopreserved was 1.3 +/- 0.7 and 1.2 +/- 0.5 x 10(6)/kg, respectively. No severe adverse events were observed during the drug administration and stem cell collection. Noteworthy is, none of the patients showed a significant modification of liver function.


CONCLUSIONS
Our study demonstrates that G-CSF administration and BMSC collection from the peripheral blood is possible and safe in patients with liver cirrhosis. The optimal dose to mobilize BMSC in cirrhotics is 15 microg/kg/day. At this dose, G-CSF does not seem to modify the residual liver function in cirrhotic patients.
Lorenzini
S
S
Department of Internal Medicine, Cardioangiology and Hepatology, University of Bologna, Bologna, Italy.
Isidori
A
A
Catani
L
L
Gramenzi
A
A
Talarico
S
S
Bonifazi
F
F
Giudice
V
V
Conte
R
R
Baccarani
M
M
Bernardi
M
M
Forbes
S J
SJ
Lemoli
R M
RM
Andreone
P
P
D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D018952:Antigens, CD34; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D005260:Female; D006023:Glycoproteins; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006801:Humans; D007937:Leukapheresis / Q000379:methods*; D008103:Liver Cirrhosis / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010455:Peptides; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D016896:Treatment Outcome
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D016179:Granulocyte Colony-Stimulating Factor