AMD3100 synergizes with G-CSF to mobilize repopulating stem cells in Fanconi anemia knockout mice

Pulliam, Anna C.; Hobson, Michael J.; Ciccone, Samantha; Li, Yan; Chen, Shi; Srour, Edward F.; Yang, Feng Chun; Broxmeyer, Hal E.; Clapp, D. Wade

doi:10.1016/j.exphem.2008.03.016

Cited by 34 publications

(23 citation statements)

References 45 publications

(32 reference statements)

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“…Doses of 5 to 10 mg/kg are routinely administered to adult mice for acute mobilization of hematopoietic progenitor cells. 28,43,44 BecauseAMD3100 has a short half-life in vivo (3.6 hours in healthy humans 45 ), an increased dose was used to antagonize CXCR4 activity long enough to effect a change in the developing retinal vasculature. Although AMD3100 has been reported to be highly specific to CXCR4, a recent report suggests that it may also bind the other known SDF-1 receptor, CXCR7.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

Strasser¹,

Kaminker²,

Tessier‐Lavigne³

2010

Blood

247

226

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The development of the vertebrate vascular system is mediated by both genetic patterning of vessels and by angiogenic sprouting in response to hypoxia. Both of these processes depend on the detection of environmental guidance cues by endothelial cells. A specialized subtype of endothelial cell known as the tip cell is thought to be involved in the detection and response to these cues, but the molecular signaling pathways used by tip cells to mediate tissue vascularization remain largely uncharacterized. To identify genes critical to tip cell function, we have developed a method to isolate them using laser capture microdissection, permitting comparison of RNA extracted from endothelial tip cells with that of endothelial stalk cells using microarray analysis. Genes enriched in tip cells include ESM-1, angiopoietin-2, and SLP-76. CXCR4, a receptor for the chemokine stromal-cell derived factor-1, was also identified as a tip cell-enriched gene, and we provide evidence for a novel role for this receptor in mediating tip cell morphology and vascular patterning in the neonatal retina. IntroductionDuring embryogenesis, the vertebrate circulatory system develops through the overlapping processes of vasculogenesis and angiogenesis. Vasculogenesis is the migration and differentiation of endothelial cells from hematopoietic precursors. Angiogenesis involves the sprouting of blood vessel networks and their maturation into an organized, functional circulatory system. 1,2 Many aspects of angiogenesis are also recapitulated in the adult during normal conditions, such as pregnancy, and pathologic situations, such as inflammation and cancer. 3 An understanding of the molecular mechanisms that govern this process is critical for the development of novel proangiogenic and antiangiogenic therapeutics.A specialized subset of endothelial cells known as tip cells is thought to mediate vessel growth and patterning. Tip cells are found at the growing end of a nascent vascular sprout and are characterized by abundant and dynamic filopodia. These filopodia are thought to detect cues in the local environment and translate them into directed motility. 4,5 Tip cells are responsive to angiogenic factors, such as vascular endothelial growth factor-A (VEGF-A), 6 as well as classic axon guidance factors, such as netrin-1. 7 The generation of new tip cells is limited by the activity of Delta-like 4 (Dll4), [8][9][10][11] which is specifically up-regulated in tip cells. 12 Signaling of Dll4 through Notch receptors on adjacent cells has been proposed to inhibit their development into tip cells. 13 Despite these advances, the mechanisms that may promote or mediate the generation of new tip cells remain incompletely understood.Recently, endothelial tip cells have become a topic of intense scrutiny, 3 but many critical questions remain about their function and how they may differ from neighboring stalk cells. Expression of several genes, including VEGF receptor 2 (VEGFR2), 6 Dll4, PDGF-B, 6 and VEGFR3, 14 has been shown to be higher in retinal tip cel...

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Section: Discussionmentioning

confidence: 99%

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

Strasser¹,

Kaminker²,

Tessier‐Lavigne³

2010

Blood

247

226

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“…hematopoietic progenitor stem cells (from the femoral bone marrow) in mice and humans [30]; and hematopoietic stem cells in Fanconi anemia knockout mice [31].…”

Section: Page 7 Of 30mentioning

confidence: 99%

The AMD3100 story: The path to the discovery of a stem cell mobilizer (Mozobil)

Clercq

2009

Biochemical Pharmacology

254

212

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“…Furthermore, patients receiving G-CSF-mobilized PBSCs have an increased incidence of chronic graft-versus-host disease (GVHD) following allogeneic transplantation (8). In addition, because older individuals or patients with Fanconi anemia (FA) show poor HSPC mobilization in response to G-CSF (9,10), it is necessary to tailor mobilization regimens to the individual clinical situation. Patients whose bone marrow has been damaged by extensive chemotherapy and radiation therapy also respond poorly to conventional mobilization regimens.…”

Section: Introductionmentioning

confidence: 99%

The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells

Kook¹,

Cho²,

Lee³

et al. 2013

J. Clin. Invest.

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Hematopoietic stem progenitor cells (HSPCs) are present in very small numbers in the circulating blood in steady-state conditions. In response to stress or injury, HSPCs are primed to migrate out of their niche to peripheral blood. Mobilized HSPCs are now commonly used as stem cell sources due to faster engraftment and reduced risk of posttransplant infection. In this study, we demonstrated that a nucleotide sugar, UDP-glucose, which is released into extracellular fluids in response to stress, mediates HSPC mobilization. UDP-glucosemobilized cells possessed the capacity to achieve long-term repopulation in lethally irradiated animals and the ability to differentiate into multi-lineage blood cells. Compared with G-CSF-mobilized cells, UDP-glucose-mobilized cells preferentially supported long-term repopulation and exhibited lymphoid-biased differentiation, suggesting that UDP-glucose triggers the mobilization of functionally distinct subsets of HSPCs. Furthermore, co-administration of UDP-glucose and G-CSF led to greater HSPC mobilization than G-CSF alone. Administration of the antioxidant agent NAC significantly reduced UDP-glucose-induced mobilization, coinciding with a reduction in RANKL and osteoclastogenesis. These findings provide direct evidence demonstrating a potential role for UDP-glucose in HSPC mobilization and may provide an attractive strategy to improve the yield of stem cells in poor-mobilizing allogeneic or autologous donors.

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AMD3100 synergizes with G-CSF to mobilize repopulating stem cells in Fanconi anemia knockout mice

Cited by 34 publications

References 45 publications

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

Microarray analysis of retinal endothelial tip cells identifies CXCR4 as a mediator of tip cell morphology and branching

The AMD3100 story: The path to the discovery of a stem cell mobilizer (Mozobil)

The nucleotide sugar UDP-glucose mobilizes long-term repopulating primitive hematopoietic cells

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