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/
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
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.