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dc.contributor.authorSchofield, Karen P
dc.contributor.authorHumphries, M J
dc.contributor.authorDe Wynter, Erika A
dc.contributor.authorTesta, Nydia G
dc.contributor.authorGallagher, John T
dc.date.accessioned2010-02-23T11:12:19Z
dc.date.available2010-02-23T11:12:19Z
dc.date.issued1998-05-01
dc.identifier.citationThe effect of alpha4 beta1-integrin binding sequences of fibronectin on growth of cells from human hematopoietic progenitors. 1998, 91 (9):3230-8 Blooden
dc.identifier.issn0006-4971
dc.identifier.pmid9558378
dc.identifier.urihttp://hdl.handle.net/10541/92714
dc.description.abstractHighly regulated interactions between adhesion receptors on progenitor cells and their extracellular matrix ligands are essential for the control of hematopoiesis in bone marrow stroma. We have examined the relationship between alpha4beta1-integrin-mediated adhesion and growth of CD34(+) cells by assessing their adhesive and migratory patterns of proliferation in a mixture of hematopoietic growth factors in the presence of different recombinant fragments of the HepII/IIICS region of fibronectin. CD34(+) cells were isolated from cord blood and placed in culture wells containing serum-free medium and growth factors. Wells were precoated with either the H120 fragment of fibronectin, which contains three alpha4beta1-integrin binding sites, or the H0 fragment, which lacks the two highest affinity alpha4beta1 binding sequences. Proliferation of single cells of CD34(+)38(+)DR+ and CD34(+)38(-)DR+ phenotypes occurred in contact with the H120 substrate and was associated with migration. Larger numbers of cells were used to quantitate proliferative responses. Cells growing in wells coated with H120 formed attachments to the base of the wells throughout the culture period. Higher total cell counts were consistently found in wells coated with H120 compared with H0 and bovine serum albumin controls. The difference was first apparent at day 8 of culture and reached a maximum at days 11 through 13, when expansion with H120 was a mean of 1.8-fold higher than that seen with H0 (P
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subject.meshADP-ribosyl Cyclase
dc.subject.meshAntigens, CD
dc.subject.meshAntigens, CD34
dc.subject.meshAntigens, CD38
dc.subject.meshAntigens, Differentiation
dc.subject.meshBinding Sites
dc.subject.meshCell Adhesion
dc.subject.meshCell Division
dc.subject.meshCell Movement
dc.subject.meshCloning, Molecular
dc.subject.meshFetal Blood
dc.subject.meshFibronectins
dc.subject.meshHematopoietic Stem Cells
dc.subject.meshHumans
dc.subject.meshIntegrin alpha4beta1
dc.subject.meshIntegrins
dc.subject.meshMembrane Glycoproteins
dc.subject.meshNAD+ Nucleosidase
dc.subject.meshPeptide Fragments
dc.subject.meshProtein Binding
dc.subject.meshReceptors, Fibronectin
dc.subject.meshReceptors, Lymphocyte Homing
dc.subject.meshTime Factors
dc.titleThe effect of alpha4 beta1-integrin binding sequences of fibronectin on growth of cells from human hematopoietic progenitors.en
dc.typeArticleen
dc.contributor.departmentDepartments of Medical Oncology and Experimental Haematology, Paterson Institute for Cancer Research, Manchester, UK.en
dc.identifier.journalBlooden
html.description.abstractHighly regulated interactions between adhesion receptors on progenitor cells and their extracellular matrix ligands are essential for the control of hematopoiesis in bone marrow stroma. We have examined the relationship between alpha4beta1-integrin-mediated adhesion and growth of CD34(+) cells by assessing their adhesive and migratory patterns of proliferation in a mixture of hematopoietic growth factors in the presence of different recombinant fragments of the HepII/IIICS region of fibronectin. CD34(+) cells were isolated from cord blood and placed in culture wells containing serum-free medium and growth factors. Wells were precoated with either the H120 fragment of fibronectin, which contains three alpha4beta1-integrin binding sites, or the H0 fragment, which lacks the two highest affinity alpha4beta1 binding sequences. Proliferation of single cells of CD34(+)38(+)DR+ and CD34(+)38(-)DR+ phenotypes occurred in contact with the H120 substrate and was associated with migration. Larger numbers of cells were used to quantitate proliferative responses. Cells growing in wells coated with H120 formed attachments to the base of the wells throughout the culture period. Higher total cell counts were consistently found in wells coated with H120 compared with H0 and bovine serum albumin controls. The difference was first apparent at day 8 of culture and reached a maximum at days 11 through 13, when expansion with H120 was a mean of 1.8-fold higher than that seen with H0 (P</= .0001). The greatest expansion (2.25-fold) with H120 compared with H0 was seen when the growth factor concentrations were reduced to 1/16 of the standard levels (P </= .001). The increase in total cell numbers was not at the expense of CD34(+) cells as numbers of these were similar in H120 and control cultures. These results provide evidence for synergy between growth factors and integrins that may be relevant to understanding hematopoiesis in marrow stroma.


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