Gehling UM, Willems M, Schlagner K, Benndorf RA, Dandri M, Petersen J, Sterneck M, Pollok JM, Hossfeld DK, Rogiers X. Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis. World J Gastroenterol 2010; 16(2): 217-224 [PMID: 20066741 DOI: 10.3748/wjg.v16.i2.217]
Corresponding Author of This Article
Ursula M Gehling, MD, Department of Hepatobiliary Surgery and Transplant Surgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. gehling@uke.uni-hamburg.de
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World J Gastroenterol. Jan 14, 2010; 16(2): 217-224 Published online Jan 14, 2010. doi: 10.3748/wjg.v16.i2.217
Mobilization of hematopoietic progenitor cells in patients with liver cirrhosis
Ursula M Gehling, Marc Willems, Kathleen Schlagner, Ralf A Benndorf, Maura Dandri, Jörg Petersen, Martina Sterneck, Joerg-Matthias Pollok, Dieter K Hossfeld, Xavier Rogiers
Ursula M Gehling, Marc Willems, Martina Sterneck, Joerg-Matthias Pollok, Xavier Rogiers, Department of Hepatobiliary Surgery and Transplant Surgery, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Kathleen Schlagner, Maura Dandri, Jörg Petersen, Dieter K Hossfeld, Department of Medicine, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Ralf A Benndorf, Institute of Experimental and Clinical Pharmacology and Toxicology, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
Xavier Rogiers, Gent University Hospital and Medical School, 9000 Gent, Belgium
Author contributions: Gehling UM, Willems M and Rogiers X designed the study; Gehling UM and Schlagner K performed the research; Benndorf RA, Dandri M and Petersen J contributed to analysis and interpretation of the data; Sterneck M, Pollok JM and Hossfeld DK contributed to data acquisition; Gehling UM wrote the manuscript.
Supported by Grants from the Erich und Gertrud Roggenbuck Foundation, Hamburg and the Werner Otto Foundation, Hamburg
Correspondence to: Ursula M Gehling, MD, Department of Hepatobiliary Surgery and Transplant Surgery, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. gehling@uke.uni-hamburg.de
Telephone: +49-40-428039586 Fax: +49-40-428035898
Received: November 9, 2009 Revised: November 27, 2009 Accepted: December 4, 2009 Published online: January 14, 2010
Abstract
AIM: 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.
CONCLUSION: 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.
