[HTML][HTML] Efficient transduction and engraftment of G-CSF-mobilized peripheral blood CD34+ cells in nonhuman primates using GALV-pseudotyped gammaretroviral …

BC Beard, P Mezquita, JC Morris, HP Kiem - Molecular Therapy, 2006 - cell.com
BC Beard, P Mezquita, JC Morris, HP Kiem
Molecular Therapy, 2006cell.com
The optimal stem cell source for stem cell gene therapy has yet to be determined. Most large-
animal studies have utilized peripheral blood or marrow-derived cells collected after
administration of granulocyte colony-stimulating factor (G-SCF) and stem cell factor (SCF);
however, SCF is unavailable for clinical use in the United States and the European Union. A
recent study in a competitive repopulation assay in the rhesus macaque showed very
inefficient marking of G-CSF-mobilized (G/only) peripheral blood (G-PBSC) CD34+ cells …
Abstract
The optimal stem cell source for stem cell gene therapy has yet to be determined. Most large-animal studies have utilized peripheral blood or marrow-derived cells collected after administration of granulocyte colony-stimulating factor (G-SCF) and stem cell factor (SCF); however, SCF is unavailable for clinical use in the United States and the European Union. A recent study in a competitive repopulation assay in the rhesus macaque showed very inefficient marking of G-CSF-mobilized (G/only) peripheral blood (G-PBSC) CD34+ cells relative to G-CSF and SCF-mobilized cells using vectors with an amphotropic pseudotype. Because G-PBSC would be the preferred target cell population for most clinical stem cell gene therapy applications, we asked whether we could achieve efficient transduction and engraftment of G-PBSC using Phoenix-GALV-pseudotyped vectors. We transplanted three baboons with G/only mobilized CD34+ cells transduced with GALV-pseudotyped retroviral vectors. We observed high-level, persistent engraftment of gene-modified G-PBSC in all animals with gene marking levels in granulocytes up to 60%. We analyzed amphotropic (PIT2) and GALV (PIT1) receptor expression in G/only cells and found preferential expression of PIT1 after G/only, which may explain the inferior results with amphotropic pseudotypes. These findings demonstrate that high stem cell gene transfer levels can be achieved using G-CSF-mobilized PBSC with Phoenix-GALV-pseudotyped vectors.
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