Preclinical experience with amd3100 for mobilization of hematopoietic stem and progenitor cells

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations

Abstract

The SDF-1/CXCL12 CXCR4 axis is involved in a number of functional activities of hematopoietic stem (HSC) and progenitor cells (HPC). This includes migration, chemotaxis, homing, and survival. AMD3100, also known as Plerixafor or Mozobil, is a small molecular weight Bicyclam known to specifi cally antagonize the binding of stromal cell-derived factor-1 (SDF-1)/CXCL12 to one of its receptors, CXCR4. This chapter reviews preclinical studies demonstrating the fi rst proofof- principle that AMD3100 is a potent and rapid mobilizer of HSC/HPC to the blood in mice and that AMD3100 synergizes with the main HSC/HPC-mobilizing agent, granulocyte-colony-stimulating factor (G-CSF) to greatly enhance G-CSFinduced mobilization of HSC/HPC. Preclinical studies, which led to clinical evaluation of AMD3100 were possible in part because of the nonspecies specifi city of AMD3100 which allowed for mobilization studies fi rst in mice, and subsequently in dogs and monkeys, including transplantation of the mobilized cells into conditioned animals of their own species. Preclinical studies in higher animals and the fi rst, and subsequent human clinical studies with AMD3100 are described. Also, discussed are the use of AMD3100 with other mobilizing agents, such as GRO- b, and potential uses of AMD3100 to enhance engraftment of HSC, to treat infl ammatory disorders involving SDF-1/CXCL12-CXCR4 interactions, and as a tool to dissect out cell and intracellular events mediated by SDF-1/CXCL12.

Original languageEnglish (US)
Title of host publicationNovel Developments in Stem Cell Mobilization
Subtitle of host publicationFocus on CXCR4
PublisherSpringer US
Pages3-22
Number of pages20
ISBN (Electronic)9781461419600
ISBN (Print)9781461419594
DOIs
StatePublished - Jan 1 2012

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Keywords

  • AMD3100
  • G-CSF
  • Mobilization
  • Progenitor cells
  • Stem cells

ASJC Scopus subject areas

  • Medicine(all)

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