ArticleBlood advances2017
Two distinct CXCR4 antagonists mobilize progenitor cells in mice by different mechanisms.
Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies.Stem cell research & therapy · 2021Pooled it
- Drug-based mobilisation of mesenchymal stem/stromal cells improves cardiac function post myocardial infarction.Disease models & mechanisms · 2023Article
- GPC-100, a novel CXCR4 antagonist, improves in vivo hematopoietic cell mobilization when combined with propranolol.PloS one · 2023Article
- Article
- Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization.Communications biology · 2021Article
- Unrestrained GαFrontiers in immunology · 2021Article
- AMD3100 redosing fails to repeatedly mobilize hematopoietic stem cells in the nonhuman primate and humanized mouse.Experimental hematology · 2021Article
- Pharmacological tools to mobilise mesenchymal stromal cells into the blood promote bone formation after surgery.NPJ Regenerative medicine · 2020Article
- Article
- HIF prolyl hydroxylase inhibitor FG-4497 enhances mouse hematopoietic stem cell mobilization via VEGFR2/KDR.Blood advances · 2019Article
- CXCR4 knockdown prevents inflammatory cytokine expression in macrophages by suppressing activation of MAPK and NF-κB signaling pathways.Cell & bioscience · 2019Article
- CXCR4, the master regulator of neutrophil trafficking in homeostasis and disease.European journal of clinical investigation · 2018Review
- A mouse model for evaluation of efficacy and concomitant toxicity of anti-human CXCR4 therapeutics.PloS one · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Pharmacological mobilization of hematopoietic progenitor cells (HPCs) is used clinically to harvest HPCs for bone marrow transplants. It is now widely accepted that the CXCR4:CXCL12 chemokine axis plays a critical role in the retention of HPCs in the bone marrow, and CXCR4 antagonists have been developed for their mobilization. The first of this class of drugs to be US Food and Drug Administration-approved was the bicyclam AMD3100. In addition to mobilizing HPCs and leukocytes in naïve mice, AMD3100 has been shown to mobilize mesenchymal progenitor cells (MPCs) in vascular endothelial growth factor (VEGF-A) pretreated mice. AMD3100 binds to the transmembrane region of CXCR4 and is thought to mobilize HPCs by reversing the gradient of CXCL12 across the bone marrow endothelium. Consistent with this hypothesis, our data show that selective neutralization of CXCL12, with chalcone 4-phosphate (C4P), inhibited AMD3100-stimulated mobilization of HPCs and leukocytes in naïve mice and MPCs in VEGF-A pretreated mice. In contrast it is shown here that the CXCR4 antagonist KRH3955 that binds to the extracellular loop of CXCR4 does not reverse the CXCL12 chemokine gradient. However, this drug efficiently mobilizes HPCs, a response that is not inhibited by C4P. In contrast, KRH3955 does not mobilize MPCs in VEGF-A pretreated mice. These data suggest that CXCR4 antagonists that bind to distinct regions of the receptor mobilize progenitor cells by distinct molecular mechanisms.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.