Insights into the biology of mobilized hematopoietic stem/progenitor cells through innovative treatment schedules of the CXCR4 antagonist AMD3100

Exp Hematol. 2009 Mar;37(3):402-15.e1. doi: 10.1016/j.exphem.2008.10.017. Epub 2009 Jan 20.


Objective: The CXCR4 antagonist AMD3100 mobilizes hematopoietic stem/progenitor cells (HSPC) in several species. Few data are available on the biology of HSPC mobilized with AMD3100 as single agent. To further study the kinetics and properties of AMD3100-mobilized HSPC, and to explore the size of mobilizable pools of HSPC targeted by AMD3100, we studied the effect of a continuous infusion scheme with saturating doses of AMD3100 [AMDi].

Materials and methods: Using established procedures, we evaluated mice mobilized with AMD3100, or those transplanted with AMD3100-mobilized HSPC.

Results: Relative to single-bolus AMD3100 [AMDb], the number of circulating CFU-C or CRU was dramatically higher after [AMDi]. During [AMDi], circulating CFU-C accumulated slowly, but after its discontinuation, CFU-C disappeared rapidly. Compared to bone marrow (BM)-c-kit(+) cells, AMD3100-mobilized (AMDb or AMDi) c-kit(+) cells showed reduced expression of several cytoadhesion molecules, similar to granulocyte colony-stimulating factor-mobilized c-kit(+) cells. In contrast to the latter, expression of CXCR4 and CD26 were not reduced on AMD3100-mobilized c-kit(+) cells. BM homing of [AMDi]-mobilized CFU-C was >50% increased over normal BM-CFU-C. Hematopoietic recovery after transplantation of [AMDi]-mobilized peripheral blood was comparable to that of continuous infusion granulocyte colony-stimulating factor-mobilized peripheral blood. AMD3100-mobilized HSPC were predominantly in G(0), and partial bromodeoxyuridine-labeling experiments documented underrepresentation of labeled cells (<5%) among [AMDb]-mobilized c-kit(+) cells, suggesting that cycling cells in BM, or those that recently completed cell cycle, are not targeted for mobilization by AMD3100.

Conclusions: Our data demonstrate that [AMDi] is an efficacious mobilization scheme fully supporting transplantation demands and expands previous knowledge about properties and size of AMD3100-sensitive BM-HSPC pools.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines
  • Bone Marrow Cells
  • Cell Count
  • Cell Movement
  • Cyclams
  • Hematopoietic Stem Cell Mobilization / methods*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Heterocyclic Compounds / administration & dosage
  • Heterocyclic Compounds / pharmacology*
  • Mice
  • Peripheral Blood Stem Cell Transplantation
  • Receptors, CXCR4 / antagonists & inhibitors


  • Benzylamines
  • Cyclams
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • plerixafor