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/

Citation
Nj. Elwood et al., 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/, Blood, 88(12), 1996, pp. 4452-4462
Citations number
51
Categorie Soggetti
Hematology
Journal title
BloodACNP
ISSN journal
00064971
Volume
88
Issue
12
Year of publication
1996
Pages
4452 - 4462
Database
ISI
SICI code
0006-4971(1996)88:12<4452:RTOHPC>2.0.ZU;2-W
Abstract
The clinical application of gene transfer is hindered by the availabil ity of the multipotential stem cells and the difficulty in obtaining e fficient retroviral transduction. To assess potential means by which g ene 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 effic iency of cells mobilized with G-CSF plus stem cell factor (SCF) in a c ohort of patients randomized to receive either one or two growth facto rs 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 comb ination of SCF plus G-CSF, However, pretreatment of patients with G-CS F with or without SCF did not enhance the retroviral infectability of growth factor-mobilized progenitor cells. The effect of the growth fac tor, Flk-2/Flt3 ligand (FL), was also examined with respect to retrovi ral transduction efficiency of human progenitor cells. FL plus IL-3 in vitro increased the retroviral transduction efficiency up to eightfol d 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-t herapy studies and improving the efficiency of gene transfer. (C) 1996 by The American Society of Hematology.