Treatment of circulating CD34+ cells with SDF-1α or anti-CXCR4 antibody enhances migration and NOD/SCID repopulating potential

Plett, P. Artur; Frankovitz, Stacy M.; Wolber, Frances M.; Abonour, Rafat; Orschell-Traycoff, Christie M.

doi:10.1016/s0301-472x(02)00880-9

Cited by 48 publications

(45 citation statements)

References 53 publications

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“…These studies nevertheless show that the property governing the superior homing of MPB HPC to marrow is independent of accompanying mature leukocytes or of certain host conditions and lies within a cell population which is enriched for HPC. Although several studies have shown [45] or implied [46][47][48] the potential for superior marrow homing of MPB HPC, opposing views, showing similar [49] or even inferior [10] homing of MPB, have also been reported. Reasons for the discrepancies are not clear but may include insufficient sample size [49] and immunophenotypic instead of functional definition of HPC.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

Bönig

Priestley

Oehler

et al. 2007

Experimental Hematology

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Objective-Faster engraftment of G-CSF mobilized peripheral blood (MPB) transplants compared to steady-state bone marrow (ssBM) is well documented and clinically relevant. A number of different factors likely contribute to this outcome. In the present study we explored whether independent of cell number there are intrinsic differences in the efficiency of progenitor cell homing to marrow between MPB and ssBM. Methods-Mobilization was achieved by continuous infusion of G-CSF alone or in combination with other mobilizing agents.In vivo homing assays, in vitro migration assays, gene expression analysis and flow cytometry were utilized to compare homing-related in vivo and in vitro properties of MPB and ssBM HPC.Results-Marrow homing of murine MPB HPC, generated by different mobilizing schemes, was reproducibly significantly superior to that of ssBM, in lethally irradiated as well as in non-irradiated hosts. This phenotype was independent of MMP9, selectins, β2-and α4-integrins. Superior homing was also observed for human MPB HPC transplanted into NOD/SCIDβ2microglobulin-/-recipients. Inhibition of HPC migration abrogated the homing advantage of MPB but did not affect homing of ssBM HPC, whereas enhancement of motility by CD26 inhibition improved marrow homing only of ssBM HPC. Enhanced SDF-1 dependent chemotaxis and low CD26 expression on MPB HPC were identified as potential contributing factors. Significant contributions of the putative alternative SDF-1 receptor, RDC1, were unlikely based on gene expression data. Conclusion-The data suggest increased motility as a converging end point of complex changes seen in MPB HPC which is likely responsible for their favorable homing.

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Section: Discussionmentioning

confidence: 99%

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

Bönig

Priestley

Oehler

et al. 2007

Experimental Hematology

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“…[24][25][26] Whether in vivo treatments with polyclonal antibodies versus different CXCR4 antagonistic molecules with potentially different modes of action could account for these differences is difficult to discern at this point and further experimentation is warranted. On a relevant vein, data with in vitro anti-CXCR4 antibody treatments are inconsistent [61][62][63][64] and at odds with studies using Ptx-treated cells in homing experiments of murine BM, 60 murine fetal liver cells, 65 or human CD34 ϩ cells. 62 Collectively, the weight of the evidence suggests that CXCR4/SDF-1 signaling may not be crucial for the initial anchoring of transplanted cells to endothelial cells within BM, but their subsequent retention within BM is greatly dependent on CXCR4/SDF-1 signaling.…”

Section: Discussionmentioning

confidence: 99%

The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization

Papayannopoulou

Priestley

Bönig

et al. 2003

Blood

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The directed migration of mature leukocytes to inflammatory sites and the lymphocyte trafficking in vivo are dependent on G protein-coupled receptors and delivered through pertussis toxin (Ptx)-sensitive G i -protein signaling. In the present study, we explored the in vivo role of G-protein signaling on the redistribution or mobilization of hematopoietic stem/progenitor cells (HPCs). A single injection of Ptx in mice elicits a long-lasting leukocytosis and a progressive increase in circulating colonyforming unit-culture (CFU-C) and colonyforming unit spleen (CFU-S). We found that the prolonged effect is sustained by a continuous slow release of Ptx bound to red blood cells or other cells and is potentially

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“…52 Brief exposure of mobilized human peripheral blood or peripheral blood CD34 þ cells to 100 ng/ml SDF-1 or to activating anti-CXCR4 antibody augmented their in vitro migration and NOD/SCID repopulating potential. 53 Taken together, the results strongly suggest that treatment of human hematopoietic stem and progenitor cells with low concentrations of SDF-1 during the transduction process increases their engraftment potential as well. SDF-1 may thus have multifaceted benefits for cellular and gene therapy.…”

Section: Discussionmentioning

confidence: 67%

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

et al. 2003

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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.

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Treatment of circulating CD34+ cells with SDF-1α or anti-CXCR4 antibody enhances migration and NOD/SCID repopulating potential

Cited by 48 publications

References 53 publications

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

Hematopoietic Progenitor Cells (HPC) from Mobilized Peripheral Blood Display Enhanced Migration and Marrow Homing Compared to Steady-State Bone Marrow HPC

The role of G-protein signaling in hematopoietic stem/progenitor cell mobilization

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

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