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  • Spotlight Review
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Spotlight on Stem Cell Homing and Mobilisation

Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4

Leukemia volume 26, pages 34–53 (2012)Cite this article

Abstract

Successful hematopoietic stem cell transplant requires the infusion of a sufficient number of hematopoietic stem/progenitor cells (HSPCs) that are capable of homing to the bone marrow cavity and regenerating durable trilineage hematopoiesis in a timely manner. Stem cells harvested from peripheral blood are the most commonly used graft source in HSCT. Although granulocyte colony-stimulating factor (G-CSF) is the most frequently used agent for stem cell mobilization, the use of G-CSF alone results in suboptimal stem cell yields in a significant proportion of patients. Both the chemokine receptor CXCR4 and the integrin α4β1 (very late antigen 4 (VLA-4)) have important roles in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of CXCR4 or VLA-4 with their ligands results in the rapid and reversible mobilization of hematopoietic stem cells into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the development of small-molecule CXCR4 and VLA-4 inhibitors and how they may improve the utility and convenience of peripheral blood stem cell transplantation.

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Acknowledgements

We apologize to colleagues whose work we are not able to discuss because of space limitations. This work was supported in part by research funding from The Barnes Jewish Foundation (St Louis, MO, USA), Genzyme Corporation (Cambridge, MA, USA) and National Institutes of Health Grant R21 CA141523-01 to JFD. The project described was also supported by Grant Nos. 1 UL1 RR024992-01, 1 TL1 RR024995-01 and 1 KL2 RR 024994-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

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  1. Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO, USA

    M P Rettig, G Ansstas & J F DiPersio

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MPR and JFD have received honoraria from Genzyme Corp.

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Rettig, M., Ansstas, G. & DiPersio, J. Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4 and VLA-4. Leukemia 26, 34–53 (2012). https://doi.org/10.1038/leu.2011.197

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