ArticleHaematologica2009
Ex vivo expansion of hematopoietic progenitor cells is associated with downregulation of alpha4 integrin- and CXCR4-mediated engraftment in NOD/SCID beta2-microglobulin-null mice.
Article in Haematologica, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- The Biological and Clinical Relevance of G Protein-Coupled Receptors to the Outcomes of Hematopoietic Stem Cell Transplantation: A Systematized Review.International journal of molecular sciences · 2019Pooled it
- Immunophenotypic and Functional Interindividual Variability in Banked Cord Blood Cells: Insights for Advanced Therapies.International journal of molecular sciences · 2025Article
- Hypoxia and low-dose inflammatory stimulus synergistically enhance bone marrow mesenchymal stem cell migration.Cell proliferation · 2017Article
- GSK-3β inhibition promotes early engraftment of ex vivo-expanded haematopoietic stem cells.Cell proliferation · 2014Article
- Ex vivo expansion of umbilical cord blood: where are we?International journal of hematology · 2012Review
- Article
- Co-culture of hematopoietic stem cells with mesenchymal stem cells increases VCAM-1-dependent migration of primitive hematopoietic stem cells.International journal of hematology · 2011Article
- Impaired CXCR4 expression and cell engraftment of bone marrow-derived cells from aged atherogenic mice.Atherosclerosis · 2011Article
- Targeting stem cell niches and trafficking for cardiovascular therapy.Pharmacology & therapeutics · 2011Review
- Cord blood stem cell expansion is permissive to epigenetic regulation and environmental cues.Experimental hematology · 2009Article
- Expansion of cord blood stem cells in fibronectin-coated microfluidic bioreactor.Hematology, transfusion and cell therapyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSeveral studies indicate that ex vivo cytokine-supported expansion induces defective hematopoietic stem cell engraftment. We investigated the role of alpha4 integrin, alpha5 integrin and CXCR4 in engraftment of unmanipulated and cytokine-treated human cord blood CD34(+) cells. DESIGN AND
methodsUncultured or expanded CD34(+) cells were infused in NOD/SCID-beta(2)microglobulin-null mice. The function of alpha4, and alpha5 integrins and CXCR4 was assessed by incubating cells with specific neutralizing antibodies, prior to transplant. The activation state of alpha4 integrin was further tested by adhesion and migration assays.
resultsNeutralization of either alpha4 integrin or CXCR4 abolished engraftment of uncultured CD34(+) cells at 6 week spost-transplant, while alpha5 integrin neutralization had no significant effect. However, after short-term ex vivo culture, blocking alpha4 integrin or CXCR4 did not affect repopulating activity whereas neutralization of alpha5 integrin inhibited engraftment. Using soluble vascular cell adhesion molecule-1 binding assays, we observed that alpha4 integrin affinity in fresh CD34(+) cells was low and susceptible to stimulation while in cultured CD34(+) cells, it was high and insensitive to further activation. In addition, stromal cell-derived factor-1 stimulated migration across vascular cell adhesion molecule-1 in fresh CD34(+) cells but not in cultured CD34(+) cells.
conclusionsOur data show that ex vivo culture of hematopoietic progenitor cells is associated with downregulation of both alpha4 integrin- and CXCR4-mediated engraftment. Further investigations suggest that this is caused by supraphysiological increase of alpha4 integrin affinity, which impairs directional migration across vascular cell adhesion molecule-1 in response to stromal cell-derived factor-1. Such changes may underlie the engraftment defect of cytokine-stimulated CD34(+) cells.
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