Cytokine Expansion Culture of Cord Blood CD34
            <sup>+</sup>
            Cells Induces Marked and Sustained Changes in Adhesion Receptor and CXCR4 Expressions

Denning-Kendall, Patricia A.; Singha, Sakon; Bradley, B. A.; Hows, Jill

doi:10.1634/stemcells.21-1-61

Cited by 45 publications

(31 citation statements)

References 36 publications

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“…We examined whether our in vitro culture condition alters the expression patterns of these integrins and the receptor for SDF-1, CXCR-4, on AC133 ϩ cells isolated before and after culture, as reported by others [22]. In three independent experiments, the expression levels of LFA-1 on AC133 ϩ cells isolated after culture were significantly higher than those on freshly isolated AC133 ϩ cells, whereas the expressions of VLA-5 and VLA-4 on AC133 ϩ cells remained unchanged (Fig.…”

Section: Ex Vivo Culture Of Ac133 ؉ Cells Disturbs Their Distributionmentioning

confidence: 95%

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

et al. 2007

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Intra-bone marrow injection is a novel strategy for hematopoietic stem cell transplantation. Here, we investigated whether ex vivo culture of cord blood hematopoietic stem/ progenitor cells influences their reconstitution in bone marrow after intra-bone marrow transplantation. Freshly isolated AC133؉ cells or cells derived from AC133 ؉ cells cultured with cytokines (stem cell factor, flt-3 ligand, and thrombopoietin) for 5 days were injected into the bone marrow of the left tibia in irradiated NOD/SCID mice. In the bone marrow of the injected left tibia, the engraftment levels of human CD45 ؉ cells at 6 weeks after transplantation did not differ considerably between transplantation of noncultured and cytokine-cultured cells. However, the migration and distribution of transplanted cells to the bone marrow of other, noninjected bones were extremely reduced for cytokine-treated cells compared with noncultured cells. Similar findings were observed for engraftment of CD34 ؉ cells. Administration of granulocyte colony-stimulating factor to mice after transplantation induced the migration of cytokine-cultured cells to the bone marrow of previously aspirated bone but not to other intact bones. These data suggest that ex vivo manipulation of hematopoietic progenitor/stem cells significantly affects their migration properties to other bone marrow compartments after intra-bone marrow transplantation. Our data raise a caution for future clinical applications of the intra-bone marrow transplantation method using ex vivo-manipulated hematopoietic stem cells. STEM CELLS 2008;26:543-549 Disclosure of potential conflicts of interest is found at the end of this article.

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Section: Ex Vivo Culture Of Ac133 ؉ Cells Disturbs Their Distributionmentioning

confidence: 95%

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

et al. 2007

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“…SCF is secreted by bone marrow stroma and is known to increase CXCR4 expression (30). In KBM-5 cells, SCF alone or combined with imatinib induced minimal up-regulation of CXCR4.…”

Section: Imatinib Inhibits Cell Growth By Inducing Apoptosis and G 0 mentioning

confidence: 99%

CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells

Jin

Tabe

Konoplev

et al. 2008

Molecular Cancer Therapeutics

187

140

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Chronic myelogenous leukemia (CML) is driven by constitutively activated Bcr-Abl tyrosine kinase, which causes the defective adhesion of CML cells to bone marrow stroma. The overexpression of p210Bcr-Abl was reported to down-regulate CXCR4 expression, and this is associated with the cell migration defects in CML. We proposed that tyrosine kinase inhibitors, imatinib or INNO-406, may restore CXCR4 expression and cause the migration of CML cells to bone marrow microenvironment niches, which in turn results in acquisition of stroma-mediated chemoresistance of CML progenitor cells. In KBM5 and K562 cells, imatinib, INNO-406, or IFN-A increased CXCR4 expression and migration. This increase in CXCR4 levels on CML progenitor cells was likewise found in samples from CML patients treated with imatinib or IFN-A. Imatinib induced G 0 -G 1 cell cycle block in CML cells, which was further enhanced in a mesenchymal stem cell (MSC) coculture system. MSC coculture protected KBM-5 cells from imatinib-induced cell death. These antiapoptotic effects were abrogated by the CXCR4 antagonist AMD3465 or by inhibitor of integrin-linked kinase QLT0267. Altogether, these findings suggest that the upregulation of CXCR4 by imatinib promotes migration of CML cells to bone marrow stroma, causing the G 0 -G 1 cell cycle arrest and hence ensuring the survival of quiescent CML progenitor cells.

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“…Cord blood cultures were stimulated with an additional cytokine cocktail containing IL3, IL6, GM-CSF, SCF, and flt3 ligand. 32 Bone marrow cultures were cultivated for 24 h, cord blood cultures for 48 or 72 h before standard treatment with Colcemid. Metaphases were analyzed for G-bands using a modified GAG-banding technique as described.…”

Section: Cytogeneticsmentioning

confidence: 99%

Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability

et al. 2005

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Cytokine Expansion Culture of Cord Blood CD34 ⁺ Cells Induces Marked and Sustained Changes in Adhesion Receptor and CXCR4 Expressions

Abstract: ABSTRACT

Cited by 45 publications

References 36 publications

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells

Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability

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Cytokine Expansion Culture of Cord Blood CD34 + Cells Induces Marked and Sustained Changes in Adhesion Receptor and CXCR4 Expressions

Abstract: ABSTRACT

Cited by 45 publications

References 36 publications

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

Ex Vivo Culture of Human Cord Blood Hematopoietic Stem/Progenitor Cells Adversely Influences Their Distribution to Other Bone Marrow Compartments After Intra-Bone Marrow Transplantation

CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells

Centrosome aberrations in chronic myeloid leukemia correlate with stage of disease and chromosomal instability

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Cytokine Expansion Culture of Cord Blood CD34 ⁺ Cells Induces Marked and Sustained Changes in Adhesion Receptor and CXCR4 Expressions