Differential bone marrow hematopoietic stem cells mobilization in hepatectomized patients

J Gastrointest Surg. 2011 Aug;15(8):1459-67. doi: 10.1007/s11605-011-1541-7. Epub 2011 Apr 22.

Abstract

Background: The involvement of bone marrow hematopoietic stem cells (BMHSC) mobilization during liver regeneration from hepatectomized patients is under debate. The main aim of this study was to investigate the role of BMHSC mobilization after hepatic resection in 33 patients with liver disease.

Methods and results: Mobilization of CD34(+) BMHSC after 72 h of surgery was found in peripheral blood of some, but not all, of the hepatectomized patients. These CD34(+) cells co-expressed other stem cells markers. The patients without BMHSC mobilization showed high levels of circulating and liver tissue BMHSC (CD34(+) cells) previous to surgery. Therefore, two types of patients: "mobilizers" and "non-mobilizers" were distinguished based on the values of CD34(+) cells before and after surgery. Changes in cytokines involved in the hepatic regeneration (HGF and TGF-β), and in BMHSC mobilization process (SCF, SDF-1, IL-12, or MMP-2), were detected in both groups. In addition, a higher activation previous to surgery of the SDF-1/CXCR4 axis in liver tissue was observed in non mobilizers patients compared to mobilizer patients.

Conclusion: BMHSC mobilization seems to be associated with variations in the levels of cytokines and proteolytic enzymes involved in hepatic regeneration and bone marrow matrix degradation. Hepatectomy may be an insufficient stimulus for BMSHC mobilization. The pre-hepatectomy higher levels CD34(+) cells in peripheral blood and liver, associated to the activation of hepatic SDF-1/CXCR4 axis, suggest a BMHSC mobilization process previous to surgery in non mobilizer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD34 / metabolism*
  • Chemokine CXCL12 / blood
  • Female
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cells / metabolism*
  • Hematopoietic Stem Cells / physiology
  • Hepatectomy
  • Hepatocyte Growth Factor / blood
  • Humans
  • Interleukin-12 / blood
  • Ki-67 Antigen / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver / surgery
  • Liver Regeneration / physiology*
  • Male
  • Matrix Metalloproteinase 2 / blood
  • Middle Aged
  • Receptors, CXCR4 / blood
  • Signal Transduction / physiology*
  • Stem Cell Factor / blood
  • Transforming Growth Factor beta / blood

Substances

  • Antigens, CD34
  • Chemokine CXCL12
  • HGF protein, human
  • Ki-67 Antigen
  • Receptors, CXCR4
  • Stem Cell Factor
  • Transforming Growth Factor beta
  • Interleukin-12
  • Hepatocyte Growth Factor
  • Matrix Metalloproteinase 2