VLA-5 is expressed by mouse and human long-term repopulating hematopoietic cells and mediates adhesion to extracellular matrix protein fibronectin.

Loo, Johannes C.M. van der; Xiao, Xu; McMilin, Doug; Hashino, Kimikazu; Kato, Ikunoshin; Williams, David A.

doi:10.1172/jci3687c1

Cited by 53 publications

(73 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been suggested by different authors that VLA-5 plays a physiologic role in stem cell trafficking. 10,15,37,44 Because other studies have observed an engraftment defect of cycling stem/progenitor cells, our data may suggest that this is partly caused by increased static adhesion and impaired motility across Fn. Whether such a phenomenon applies to the interaction of cycling progenitor cells to other adhesion molecules remains the subject of further studies and should provide more detailed knowledge of the homing mechanisms of expanded HSCs.…”

Section: Discussionmentioning

confidence: 73%

“…13 Fn is recognized by 2 different ␤1 integrins expressed by HSCs: VLA-4 and VLA-5. Previous studies have highlighted a dominant role either for VLA-4 14 or for VLA-5 15 in Fn binding of HSCs. Interaction of HSCs with Fn is a tightly regulated process controlled by cytokines such as stem cell factor (SCF), interleukin-3, and thrombopoietin, [16][17][18][19] which have been reported to modulate both VLA-4 and VLA-5 during short-term ex vivo culture, influencing adhesion 20,21 and migration onto Fn-coated surfaces.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells

Giet

Bockstaele

Stefano

et al. 2002

Blood

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells

Giet

Bockstaele

Stefano

et al. 2002

Blood

View full text Add to dashboard Cite

“…VLA-4 and VLA-5 integrins have been implicated in adhesive interactions of repopulating stem cells with BM extracellular matrix and stromal cells. [54][55][56][57] Fibronectin, an abundant extracellular matrix molecule, has been studied as a prototype molecule in cell-cell and cell-matrix interactions. [58][59][60] A fibronectin-derived recombinant fragment CH-296, Retronectin, has been used as a primary tool to enhance transduction of primitive hematopoietic cells.…”

Section: Discussionmentioning

confidence: 99%

SDF-1α/CXCL12 enhances retroviral-mediated gene transfer into immature subsets of human and murine hematopoietic progenitor cells

et al. 2003

View full text Add to dashboard Cite

Genetic modification of hematopoietic stem and progenitor cells has the potential to treat diseases affecting blood cells. Oncoretroviral vectors have been used for gene therapy; however, clinical success has been limited in part by low gene transfer efficiencies. We found that the presence of stromal-derived factor 1 (SDF-1a)/CXCL12 during retroviral transduction significantly enhanced, in a dose-dependent fashion, gene transfer into immature subsets of high proliferative human and murine hematopoietic progenitor cells. Murine mononuclear bone marrow cells and purified c-Kit þ Lin À bone marrow cells were prestimulated and transduced with the bicistronic retroviral vector MIEG3 on Retronectin-coated surfaces in the presence and absence of SDF-1. SDF-1 enhanced gene transduction of murine bone marrow and c-Kit þ Lin À cells by 35 and 29%, respectively. Moreover, SDF-1 enhanced transduction of progenitors in these populations by 121 and 107%, respectively. SDF-1 also enhanced transduction of human immature subsets of high proliferative progenitors present in either nonadherent mononuclear or CD34 þ umbilical cord blood cells. Transduction of hematopoietic progenitors was further increased by preloading Retronectin-coated plates with retrovirus using low-speed centrifugation followed by increasing cell-virus interactions through brief centrifugation during the transduction procedure. These results may be of clinical relevance.

show abstract

“…15 Human hematopoietic progenitor cells bind in vitro to the RGD motif of fibronectin through interaction with α5. 16 However, contradictory data have been reported concerning the contribution of α5 in mobilization and homing in vivo. α5 neutralization does not interfere with bone marrow lodgment and retention of murine progenitor cells, 15,17 but results in significant impairment of human CD34 + cell engraftment in NOD/SCID mice, 18 albeit to a lesser degree than treatment with α4 antibody.…”

Section: Introductionmentioning

confidence: 99%

Ex vivo expansion of hematopoietic progenitor cells is associated with downregulation of 4 integrin- and CXCR4-mediated engraftment in NOD/SCID 2-microglobulin-null mice

Foguenne

Stefano²,

Giet

et al. 2009

Haematologica

View full text Add to dashboard Cite

BackgroundSeveral studies indicate that ex vivo cytokine-supported expansion induces defective hematopoietic stem cell engraftment. We investigated the role of α4 integrin, α5 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-β2microglobulin-null mice. The function of α4, and α5 integrins and CXCR4 was assessed by incubating cells with specific neutralizing antibodies, prior to transplant. The activation state of α4 integrin was further tested by adhesion and migration assays. ResultsNeutralization of either α4 integrin or CXCR4 abolished engraftment of uncultured CD34 + cells at 6 weeks post-transplant, while α5 integrin neutralization had no significant effect. However, after short-term ex vivo culture, blocking α4 integrin or CXCR4 did not affect repopulating activity whereas neutralization of α5 integrin inhibited engraftment. Using soluble vascular cell adhesion molecule-1 binding assays, we observed that α4 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 cellderived 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 α4 integrin-and CXCR4-mediated engraftment. Further investigations suggest that this is caused by supraphysiological increase of α4 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.Key words: stem cells, hematopoiesis, cell trafficking. -and CXCR4-mediated engraftment in NOD/SCID β2-microglobulin-null mice. Haematologica 2009; 94:185-194. doi: 10.3324/haematol.13206 ©2009 Ferrata Storti Foundation. This is an open-access paper. Citation: Foguenne J, Di Stefano I, Giet O, Beguin Y, and Gothot A. Ex vivo expansion of hematopoietic progenitor cells is associated with downregulation of α4 integrin Ex vivo

show abstract

VLA-5 is expressed by mouse and human long-term repopulating hematopoietic cells and mediates adhesion to extracellular matrix protein fibronectin.

Cited by 53 publications

References 0 publications

Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells

Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells

SDF-1α/CXCL12 enhances retroviral-mediated gene transfer into immature subsets of human and murine hematopoietic progenitor cells

Ex vivo expansion of hematopoietic progenitor cells is associated with downregulation of 4 integrin- and CXCR4-mediated engraftment in NOD/SCID 2-microglobulin-null mice

Contact Info

Product

Resources

About