AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis

Hal E. Broxmeyer, Giao Hangoc, Scott Cooper, Timothy Campbell, Shigeki Ito, Charlie Mantel

Research output: Chapter in Book/Report/Conference proceedingConference contribution

63 Scopus citations

Abstract

The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, are involved in a number of facets of the regulation of hematopoiesis at the level of hematopoietic stem (HSCs) and progenitor (HPCs) cells. Modulation of this ligand-receptor interaction may be of clinical utility.We now report that: (1) the CC chemokine, macrophage inflammatory protein-1α (MIP-1α/CCL3) synergizes with AMD3100 (an antagonist of the binding of SDF-1/CXCL12 to CXCR4) to rapidly mobilize HPCs to the blood of mice; moreover, the combination of granulocyte colony-stimulating factor (G-CSF) with AMD3100 and MIP-1α/CCL3, given in a specific sequence, mobilizes the greatest number of HPCs compared to any combination of two of these mobilizing agents; (2) pretreatment of recipient mice with Diprotin A, an inhibitor of CD26/Dipeptidylpeptidase IV (DPPIV), enhances the competitive HSCs repopulating capacity of untreated donor cells; (3) the survival-enhancing effects of SDF-1/CXCL12 on HPCs subjected in vitro to delayed addition of growth factors (GFs) are mediated in part through the cell cycle-related proteins p21 cip1/waf1 (as assessed using p21cip1/waf1 ?/? and +/+ mice) and Mad2 (using Mad2 +/? and +/+ mice); and (4) deletion of CD26/DPPIV on mouse bone marrow cells increases the survival-enhancing effects of SDF-1/CXCL12 on HPCs. These results demonstrate the means to increase the mobilization of HPCs, the engrafting capability of HSCs, and responsiveness of HPCs to the survival-enhancing activity of SDF-1/CXCL12, effects that may be of practical value.

Original languageEnglish (US)
Title of host publicationHematopoietic Stem Cells VI
PublisherBlackwell Publishing Inc.
Pages1-19
Number of pages19
ISBN (Print)1573316768, 9781573316767
DOIs
StatePublished - Jun 2007

Publication series

NameAnnals of the New York Academy of Sciences
Volume1106
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

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Keywords

  • AMD3100
  • CD26/DPPIV
  • CXCR4
  • Hematopoietic stem cells
  • Progenitor cells
  • SDF-1/CXCL12

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Broxmeyer, H. E., Hangoc, G., Cooper, S., Campbell, T., Ito, S., & Mantel, C. (2007). AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis. In Hematopoietic Stem Cells VI (pp. 1-19). (Annals of the New York Academy of Sciences; Vol. 1106). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1392.013