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Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist
Abstract
Improving approaches for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) mobilization is clinically important because increased numbers of these cells are needed for enhanced transplantation. Chemokine stromal cell derived factor-1 (also known as CXCL12) is believed to be involved in retention of HSCs and HPCs in bone marrow. AMD3100, a selective antagonist of CXCL12 that binds to its receptor, CXCR4, was evaluated in murine and human systems for mobilizing capacity, alone and in combination with granulocyte colony-stimulating factor (G-CSF). AMD3100 induced rapid mobilization of mouse and human HPCs and synergistically augmented G-CSF–induced mobilization of HPCs. AMD3100 also mobilized murine long-term repopulating (LTR) cells that engrafted primary and secondary lethally-irradiated mice, and human CD34+ cells that can repopulate nonobese diabetic-severe combined immunodeficiency (SCID) mice. AMD3100 synergized with G-CSF to mobilize murine LTR cells and human SCID repopulating cells (SRCs). Human CD34+ cells isolated after treatment with G-CSF plus AMD3100 expressed a phenotype that was characteristic of highly engrafting mouse HSCs. Synergy of AMD3100 and G-CSF in mobilization was due to enhanced numbers and perhaps other characteristics of the mobilized cells. These results support the hypothesis that the CXCL12-CXCR4 axis is involved in marrow retention of HSCs and HPCs, and demonstrate the clinical potential of AMD3100 for HSC mobilization.
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“Thus, antagonizing the interaction of SDF-1 with CXCR4 on HSCs has been shown to result in HSC mobilization in healthy human volunteers and in patients with multiple myeloma and non-Hodgkin’s lymphoma who had received previous chemotherapy[82,86].”
From Finding the needle in the hay stack: Hematopoietic stem cells in Fanconi anemia (2009) · cites this paper as [82]
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“One such agent, AMD 3100, is a competitive small-molecule antagonist of the interaction of stromal derived factor 1 (SDF-1) and the chemokine receptor CXCR4 [82].”
From Finding the needle in the hay stack: Hematopoietic stem cells in Fanconi anemia (2009) · cites this paper as [82]
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Metadata
- Authors
- Broxmeyer, H. E., Orschell, C. M., Clapp, D. W., Hangoc, G., Cooper, S., Plett, P. A., Liles, W. C., Li, X., Graham-Evans, B., Campbell, T. B., Calandra, G., Bridger, G., Dale, D. C., & Srour, E. F.
- Affiliations
- 1Department of Microbiology and Immunology, Indiana University School of Medicine
- 2Department of Medicine, Indiana University School of Medicine
- 7Department of Medicine, University of Washington, Seattle, WA 98195
- 3Department of Pediatrics, Indiana University School of Medicine
- 8AnorMed Inc., Langley, British Columbia, Canada, V2Y 1N5
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-04-18
- Volume
- 201
- Issue
- 8
- Pages
- 1307-1318
- ISSN
- 1540-9538
- 0022-1007
- PMC
- PMC2213145
- Cited by
- 970
- References
- 0
- Language
- en
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- Broxmeyer, H. E., Orschell, C. M., Clapp, D. W., Hangoc, G., Cooper, S., Plett, P. A., Liles, W. C., Li, X., Graham-Evans, B., Campbell, T. B., Calandra, G., Bridger, G., Dale, D. C., & Srour, E. F. (2005). Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20041385