Structural analogues of AMD3100 mobilise haematopoietic progenitor cells from bone marrow in vivo according to their ability to inhibit CXCL12 binding to CXCR4 in vitro

Summary The CXCR4 antagonist, AMD3100, stimulates a rapid increase in circulating numbers of haematopoeitic progenitor cells (HPCs) in both mice and human healthy volunteers. An in situ perfusion system of the mouse femoral bone marrow was used to provide the first direct evidence that AMD3100 mobilises HPCs from the bone marrow. Structural analogues of AMD3100 demonstrated that the ability of these compounds to mobilise HPCs in vivo correlated with their capacity to antagonise CXCR4 in vitro. This model system was also used to demonstrate additive effects of AMD3100 administered acutely, with granulocyte colony‐stimulating factor administered chronically, with respect to HPC mobilisation.