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Preclinical Experience with AMD3100 for Mobilization of Hematopoietic Stem and Progenitor Cells

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Novel Developments in Stem Cell Mobilization

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 specifically 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 first proof-of-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-CSF-induced mobilization of HSC/HPC. Preclinical studies, which led to clinical evaluation of AMD3100 were possible in part because of the nonspecies specificity of AMD3100 which allowed for mobilization studies first 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 first, and subsequent human clinical studies with AMD3100 are described. Also, discussed are the use of AMD3100 with other mobilizing agents, such as GRO-β, and potential uses of AMD3100 to enhance engraftment of HSC, to treat inflammatory disorders involving SDF-1/CXCL12–CXCR4 interactions, and as a tool to dissect out cell and intracellular events mediated by SDF-1/CXCL12.

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Acknowledgments

The studies cited in references from the author’s laboratory were supported in part by US Public Health Service RO1 Grants HL56416 and HL67384 from the US National Institutes of Health and Project 1 in PO1 HL053586 from National Heart Lung Blood Institute to HEB.

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  1. Department of Microbiology and Immunology, Indiana University School of Medicine, 950 West Walnut Street, R2-302, Indianapolis, IN, 46202-5181, USA

    Hal E. Broxmeyer PhD

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  1. Hal E. Broxmeyer PhD
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Correspondence to Hal E. Broxmeyer PhD .

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  1. , Zentrum für Tumordiagnostik und –therapi, Paracelsus-Klinik, Am Natruper Holz 69, Osnabrück, 49076, Germany

    Stefan Fruehauf

  2. Deutsches Krebsforschungszentrum (G360), Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    W. Jens Zeller

  3. Private, Cresco, 18326, Pennsylvania, USA

    Gary Calandra

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Broxmeyer, H.E. (2012). Preclinical Experience with AMD3100 for Mobilization of Hematopoietic Stem and Progenitor Cells. In: Fruehauf, S., Zeller, W., Calandra, G. (eds) Novel Developments in Stem Cell Mobilization. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1960-0_1

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