Retroviral transduction of human progenitor cells: Use of granulocyte colony-stimulating factor plus stem cell factor to mobilize progenitor cells in vivo and stimulation by Flt3/Flk-2 ligand in vitro
Details
Publication Year 1996-12-15, Volume 88, Issue #12, Page 4452-4462
Journal Title
BLOOD
Publication Type
Journal Article
Abstract
The clinical application of gene transfer is hindered by the availability of the multipotential stem cells and the difficulty in obtaining efficient retroviral transduction. To assess potential means by which gene transfer into human hemopoietic stem cells might be enhanced, the retroviral transduction efficiency of human bone marrow cells (BM) or peripheral blood progenitor cells (PBPC) was compared at multiple time points after in vivo administration of granulocyte colony-stimulating factor (G-CSF), This was further compared with the transduction efficiency of cells mobilized with G-CSF plus stem cell factor (SCF) in a cohort of patients randomized to receive either one or two growth factors and with normal BM function. Using the LNL6 retrovirus, retroviral transduction efficiencies of up to 19% were observed for both PBPC and BM (n = 26 patients). There was at least a 100-fold increase in PBPC with G-CSF alone and a further 30-fold increase in the total number of progenitor cells available for retroviral transduction using the combination of SCF plus G-CSF, However, pretreatment of patients with G-CSF with or without SCF did not enhance the retroviral infectability of growth factor-mobilized progenitor cells. The effect of the growth factor, Flk-2/Flt3 ligand (FL), was also examined with respect to retroviral transduction efficiency of human progenitor cells. FL plus IL-3 in vitro increased the retroviral transduction efficiency up to eightfold compared with results observed using other combinations of cytokines tested (P < .001). These findings have clinical implications both for increasing the number of target cells for in vivo gene-marking/gene-therapy studies and improving the efficiency of gene transfer. (C) 1996 by The American Society of Hematology.
Publisher
W B SAUNDERS CO
Keywords
MEDIATED GENE-TRANSFER; RECEPTOR TYROSINE KINASE; BONE-MARROW CELLS; C-KIT LIGAND; PERIPHERAL-BLOOD; HEMATOPOIETIC STEM; FLT3 LIGAND; GROWTH-FACTORS; G-CSF; FACTOR SYNERGIZES
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Creation Date: 1996-12-15 12:00:00
Last Modified: 0001-01-01 12:00:00
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