Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis.
OBJECTIVE
To test the hypothesis that liver cirrhosis is associated with mobilization of hematopoietic progenitor cells.


METHODS
Peripheral blood samples from 72 patients with liver cirrhosis of varying etiology were analyzed by flow cytometry. Identified progenitor cell subsets were immunoselected and used for functional assays in vitro. Plasma levels of stromal cell-derived factor-1 (SDF-1) were measured using an enzyme linked immunosorbent assay.


RESULTS
Progenitor cells with a CD133(+)/CD45(+)/CD14(+) phenotype were observed in 61% of the patients. Between 1% and 26% of the peripheral blood mononuclear cells (MNCs) displayed this phenotype. Furthermore, a distinct population of c-kit(+) progenitor cells (between 1% and 38% of the MNCs) could be detected in 91% of the patients. Additionally, 18% of the patients showed a population of progenitor cells (between 1% and 68% of the MNCs) that was characterized by expression of breast cancer resistance protein-1. Further phenotypic analysis disclosed that the circulating precursors expressed CXC chemokine receptor 4, the receptor for SDF-1. In line with this finding, elevated plasma levels of SDF-1 were present in all patients and were found to correlate with the number of mobilized CD133(+) progenitor cells.


CONCLUSIONS
These data indicate that in humans, liver cirrhosis leads to recruitment of various populations of hematopoietic progenitor cells that display markers of intrahepatic progenitor cells.
Gehling
Ursula M
UM
Department of Hepatobiliary Surgery and Transplant Surgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. gehling@uke.uni-hamburg.de
Willems
Marc
M
Schlagner
Kathleen
K
Benndorf
Ralf A
RA
Dandri
Maura
M
Petersen
Jörg
J
Sterneck
Martina
M
Pollok
Joerg-Matthias
JM
Hossfeld
Dieter K
DK
Rogiers
Xavier
X
D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D054377:Chemokine CXCL12 / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D055815:Young Adult
D000071916:AC133 Antigen; D015703:Antigens, CD; D054377:Chemokine CXCL12; D006023:Glycoproteins; D008565:Membrane Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D019718:Receptors, CXCR4; C488377:SFXN4 protein, human; D019009:Proto-Oncogene Proteins c-kit