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

By H. Broxmeyer, Christie M Orschell, D. Clapp, G. Hangoc, S. Cooper, P. Plett, W. Liles, Xiaxin Li, B. Graham-Evans, T. Campbell and 4 more. Journal of Experimental Medicine, 2005

1,164 citations recorded by the source corpus.

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.

Subfields: Hematology, Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/5119b59f92e90cb27a1b3c4c00dc6f3d5ea8568f

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Hematology

1. D. Lyden
2. Zena Werb
3. J. Talmadge
4. S. Fricker
5. B. Teicher
6. I. J. Fidler

In Immunology

1. A. Zlotnik
2. O. Yoshie
3. Caroline L. Sokol
4. Zena Werb
5. J. Griffith
6. D. Lyden
7. A. Luster
8. Pengfei Lu

In Oncology

1. A. Zlotnik
2. O. Yoshie
3. Zena Werb
4. Caroline L. Sokol
5. D. Hicklin
6. D. Lyden
7. R. Taichman
8. A. Luster

Citations in the corpus

• Human prostate cancer metastases target the hematopoietic stem cell niche to establish footholds in mouse bone marrow. (2011, methodology): “org Volume 121 Number 4 April 2011 1301 CXCL12 and its receptors, CXCR4 and CXCR7, are known to play major roles in HSC homing to the BM (17, 18) and in establishing PCa metastases in bone (3, 12, 19–21).”
• Cytokine-mediated deployment of SDF-1 induces revascularization through recruitment of CXCR4+ hemangiocytes (2006, background): “Paradoxically, other studies have suggested that inhibition of CXCR4 by proteases and the nonpeptide antagonist AMD3100 (refs”
• Chemokines and chemokine receptors: positioning cells for host defense and immunity. (2014, background): “Blockade of CXCR4 on HSCs is sufficient to prevent their bone marrow engraftment and to promote HSC mobilization in mice and humans (8, 9).”
• The chemokine system in innate immunity. (2015, background): “Developing neutrophils are retained in the BM by CXCR4 signals, and their maturation coincides with down-regulation of CXCR4, permitting mature neutrophils to enter the peripheral blood (Suratt et al. 2004; Broxmeyer et al. 2005).”
• The Chemokine Superfamily Revisited (2012, positive): “The latter therapeutic use of a CXCR4 antagonist was predicted after the observation that blocking CXCR4 resulted in release of hematopoietic stem cells from the bone marrow (Broxmeyer et al., 2005).”
• Rhythmic modulation of the hematopoietic niche through neutrophil clearance (2013, neutral): “(E) Mobilization of control (rIgG) or neutrophil-depleted mice (1A8) with AMD3100. n=5– 6 mice.”