Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist

Hal Broxmeyer, Christie Orschell, D. Clapp, Giao Hangoc, Scott Cooper, P. Artur Plett, W. Conrad Liles, Xiaxin Li, Barbara Graham-Evans, Timothy B. Campbell, Gary Calandra, Gary Bridger, David C. Dale, Edward Srour

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1307-1318
Number of pages12
JournalJournal of Experimental Medicine
Volume201
Issue number8
DOIs
StatePublished - Apr 18 2005

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Hematopoietic Stem Cells
Granulocyte Colony-Stimulating Factor
Severe Combined Immunodeficiency
Bone Marrow
Hematopoietic Stem Cell Mobilization
CXCR4 Receptors
Chemokine CXCL12
JM 3100
Chemokines
Cell Count
Transplantation
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. / Broxmeyer, Hal; Orschell, Christie; Clapp, D.; Hangoc, Giao; Cooper, Scott; Plett, P. Artur; Liles, W. Conrad; Li, Xiaxin; Graham-Evans, Barbara; Campbell, Timothy B.; Calandra, Gary; Bridger, Gary; Dale, David C.; Srour, Edward.

In: Journal of Experimental Medicine, Vol. 201, No. 8, 18.04.2005, p. 1307-1318.

Research output: Contribution to journalArticle

Broxmeyer, H, Orschell, C, Clapp, D, Hangoc, G, Cooper, S, Plett, PA, Liles, WC, Li, X, Graham-Evans, B, Campbell, TB, Calandra, G, Bridger, G, Dale, DC & Srour, E 2005, 'Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist', Journal of Experimental Medicine, vol. 201, no. 8, pp. 1307-1318. https://doi.org/10.1084/jem.20041385
Broxmeyer, Hal ; Orschell, Christie ; Clapp, D. ; Hangoc, Giao ; Cooper, Scott ; Plett, P. Artur ; Liles, W. Conrad ; Li, Xiaxin ; Graham-Evans, Barbara ; Campbell, Timothy B. ; Calandra, Gary ; Bridger, Gary ; Dale, David C. ; Srour, Edward. / Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. In: Journal of Experimental Medicine. 2005 ; Vol. 201, No. 8. pp. 1307-1318.
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