Peripheral blood stem cell mobilization: The CXCR2 ligand GROβ rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties

Louis M. Pelus, Seiji Fukuda

Research output: Contribution to journalReview article

98 Scopus citations

Abstract

Chemokines direct the movement of leukocytes, including hematopoietic stem and progenitor cells, and can mobilize hematopoietic cells from marrow to peripheral blood where they can be used for transplantation. In this review, we will discuss the stem cell mobilizing activities and mechanisms of action of GROβ, a CXC chemokine ligand for the CXCR2 receptor. GROβ rapidly mobilizes short- and long-term repopulating cells in mice and/or monkeys and synergistically enhances mobilization responses when combined with the widely used clinical mobilizer, granulocyte colony-stimulating factor (G-CSF). The hematopoietic graft mobilized by GROβ contains significantly more CD34neg, Sca-1+, c-kit+, lineageneg (SKL) cells than the graft mobilized by G-CSF. In mice, stem cells mobilized by GROβ demonstrate a competitive advantage upon long-term repopulation analysis and restore neutrophil and platelet counts significantly faster than cells mobilized by G-CSF. Even greater advantage in repopulation and restoration of hematopoiesis are observed with stem cells mobilized by the combination of GROβ and G-CSF. GROβ-mobilized SKL cells demonstrate enhanced adherence to vascular cell adhesion molecule-1 and VCAMpos endothelial cells and home more efficiently to bone marrow in vivo. The marrow homing ability of GROβ-mobilized cells is less dependent on the CXCR4/SDF-1 axis than cells mobilized by G-CSF. The mechanism of mobilization by GROβ requires active matrix metalloproteinase-9 (MMP-9), which results from release of pro-MMP-9 from peripheral blood, and marrow neutrophils, which alters the stoichiometry between pro-MMP-9 and its inhibitor tissue inhibitor of metalloproteinase-1, resulting in MMP-9 activation. The efficacy and rapid action of GROβ and lack of proinflammatory activity make it an attractive agent to supplement mobilization by G-CSF. In addition, GROβ may also have clinical mobilizing efficacy on its own, reducing the overall time and costs associated with peripheral blood stem cell transplantation.

Original languageEnglish (US)
Pages (from-to)1010-1020
Number of pages11
JournalExperimental Hematology
Volume34
Issue number8
DOIs
StatePublished - Aug 1 2006

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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