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

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

doi:10.1084/jem.20041385

Cited by 1,012 publications

(987 citation statements)

References 53 publications

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“…24 At this peak, the number of circulating colony-forming cells increased 16-fold ( Figure 1a). Bone histomorphometry revealed that unlike G-CSF or CYP, AMD3100 did not alter osteoblasts or osteoid surfaces on trabecular or endocortical bone of the metaphysis (Figures 1 b --e).…”

Section: Effect Of G-csf Cyp and Amd3100 On Osteoblasts And Bone Formentioning

confidence: 98%

“…However, whether CYP shuts down HSC niches in mouse strains such as C57BL/6 with low protease release has not been investigated. AMD3100 has been reported to mobilize HSC by directly antagonizing the CXCR4-mediated sensing of the CXCL12 chemotactic gradient in the BM that retains HSPC within this tissue, 24,25 and by promoting the release of CXCL12 from BM stromal cells into the circulation, thereby disrupting the CXCL12 gradient that retains HSC within the BM. 26 These latter findings suggest that AMD3100 may also alter HSC niches.…”

Section: Introductionmentioning

confidence: 99%

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Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation

et al. 2012

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The CXCR4 antagonist AMD3100 is progressively replacing cyclophosphamide (CYP) as adjuvant to granulocyte colonystimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) for autologous transplants in patients who failed prior mobilization with G-CSF alone. It has recently emerged that G-CSF mediates HSC mobilization and inhibits bone formation via specific bone marrow (BM) macrophages. We compared the effect of these three mobilizing agents on BM macrophages, bone formation, osteoblasts, HSC niches and HSC reconstitution potential. Both G-CSF and CYP suppressed niche-supportive macrophages and osteoblasts, and inhibited expression of endosteal cytokines resulting in major impairment of HSC reconstitution potential remaining in the mobilized BM. In sharp contrast, although AMD3100 was effective at mobilizing HSC, it did not suppress osteoblasts, endosteal cytokine expression or reconstitution potential of HSC remaining in the mobilized BM.In conclusion, although G-CSF, CYP and AMD3100 efficiently mobilize HSC into the blood, their effects on HSC niches and bone formation are distinct with both G-CSF and CYP targeting HSC niche function and bone formation, whereas AMD3100 directly targets HSC without altering niche function or bone formation.

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Section: Effect Of G-csf Cyp and Amd3100 On Osteoblasts And Bone Formentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation

et al. 2012

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“…The laminin receptor has 7 npg also been shown to play a key role in cancer metastasis [87]. Similarly, stromal cell derived factor and its receptor CXCR4 form a critical regulatory axis for HSC migration, engraftment and homing [88][89][90][91][92], and also function in the metastasis of breast, prostate and other types of cancer [73,[93][94][95][96][97][98][99][100]. Matrix metalloproteinase-9 (MMP-9), belongs to a family of MMPs that plays a critical role during cancer cell invasion [101][102][103][104], and it is also involved in HSC homing and migration [105][106][107].…”

Section: Stem Cell Niche and Tumor Migrationmentioning

confidence: 99%

Beyond tumorigenesis: cancer stem cells in metastasis

et al. 2006

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“…The concentration of soluble SDF-1 in the blood, however, increases in association with many of the conditions that induce stem/progenitor cell mobilization. Both sustained elevations of SDF-1 in NOD/SCID mice delivered by an adenoviral vector delivery system [34][35][36] , and chronic administration to the animals of SDF-1 peptide analogs 37,38 , result in mobilization of stem/ progenitor cells. In addition, increased plasma SDF-1 levels are also observed during mobilization induced by sulfated glycans 39 .…”

Section: Introductionmentioning

confidence: 99%

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

Migliaccio

Martelli

Verrucci

et al. 2008

Experimental Hematology

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Objective-To assess whether alterations in the SDF-1/CXCR4 occur in patients with primary myelofibrosis (PMF) and in Gata1 low mice, an animal model for myelofibrosis, and whether these abnormalities might account for increased stem/progenitor cell trafficking.Materials and Methods-In the mouse, SDF-1 mRNA levels were assayed in liver, spleen and marrow. SDF-1 protein levels were quantified in plasma and marrow and CXCR4 mRNA and protein levels were evaluated on stem/progenitor cells and megakaryocytes purified from the marrow. SDF-1 protein levels were also evaluated in plasma and in marrow biopsy specimens obtained from normal donors and PMF patients.Results-In Gata1 low mice, the plasma SDF-1 protein was 5-times higher than normal in younger animals. Furthermore, SDF-1 immuno-staining of marrow sections progressively increased with age. Similar abnormalities were observed in PMF patients. In fact, the plasma SDF-1 levels in PMF patients were significantly higher (by 2-fold) than normal (p<0.01) and SDF-1 immuno-staining of marrow biopsiy specimens demonstrated increased SDF-1 deposition in specific areas. In two of the patients, SDF-1 deposition was normalized by curative therapy with allogenic stem cell transplantation. Similarly to what already has been reported for PMF patients, the marrow from Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Gata1 low mice contained fewer CXCR4 pos CD117 pos cells and these cells expressed low levels of CXCR4 mRNA and protein. NIH Public AccessConclusion-Similar abnormalities in the SDF-1/CXCR4 axis are observed in PMF patients and in the Gata1 low mice model of myelofibrosis. We suggest that these abnormalities contribute to the increased stem/progenitor cell trafficking observed in this mouse model as well as patients with PMF.

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

Cited by 1,012 publications

References 53 publications

Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation

Hematopoietic stem cell mobilizing agents G-CSF, cyclophosphamide or AMD3100 have distinct mechanisms of action on bone marrow HSC niches and bone formation

Beyond tumorigenesis: cancer stem cells in metastasis

Altered SDF-1/CXCR4 axis in patients with primary myelofibrosis and in the Gata1low mouse model of the disease

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