Efficient transduction and engraftment of G-CSF-mobilized peripheral blood CD34+ cells in nonhuman primates using GALV-pseudotyped gammaretroviral vectors. 2006

Brian C Beard, and Pau Mezquita, and Julia C Morris, and Hans-Peter Kiem
Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.

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.

UI MeSH Term Description Entries
D010215 Papio A genus of the subfamily CERCOPITHECINAE, family CERCOPITHECIDAE, consisting of five named species: PAPIO URSINUS (chacma baboon), PAPIO CYNOCEPHALUS (yellow baboon), PAPIO PAPIO (western baboon), PAPIO ANUBIS (or olive baboon), and PAPIO HAMADRYAS (hamadryas baboon). Members of the Papio genus inhabit open woodland, savannahs, grassland, and rocky hill country. Some authors consider MANDRILLUS a subgenus of Papio. Baboons,Baboons, Savanna,Savanna Baboons,Baboon,Baboon, Savanna,Papios,Savanna Baboon
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005434 Flow Cytometry Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. Cytofluorometry, Flow,Cytometry, Flow,Flow Microfluorimetry,Fluorescence-Activated Cell Sorting,Microfluorometry, Flow,Cell Sorting, Fluorescence-Activated,Cell Sortings, Fluorescence-Activated,Cytofluorometries, Flow,Cytometries, Flow,Flow Cytofluorometries,Flow Cytofluorometry,Flow Cytometries,Flow Microfluorometries,Flow Microfluorometry,Fluorescence Activated Cell Sorting,Fluorescence-Activated Cell Sortings,Microfluorimetry, Flow,Microfluorometries, Flow,Sorting, Fluorescence-Activated Cell,Sortings, Fluorescence-Activated Cell
D006410 Hematopoiesis The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY). Hematopoiesis, Medullary,Haematopoiesis,Medullary Hematopoiesis
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014161 Transduction, Genetic The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE. Genetic Transduction,Genetic Transductions,Transductions, Genetic
D016179 Granulocyte Colony-Stimulating Factor A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines. Colony-Stimulating Factor, Granulocyte,G-CSF,Myeloid Growth Factor,Colony Stimulating Factor, Granulocyte,Factor, Granulocyte Colony-Stimulating,Factor, Myeloid Growth,Granulocyte Colony Stimulating Factor,Growth Factor, Myeloid
D050611 Sodium-Phosphate Cotransporter Proteins, Type III A family of highly conserved and widely expressed sodium-phosphate cotransporter proteins. They are electrogenic sodium-dependent transporters of phosphate that were originally identified as retroviral receptors in HUMANS and have been described in yeast and many other organisms. Type III Sodium-Phosphate Cotransporter Proteins,Amphoteric Virus Receptor GLVR-2,Amphotropic MuLV Receptor,Amphotropic Murine Leukemia Virus Receptor,GLVR-2 Receptor,GLVR1 Transporter Proteins,NPT1 Protein,Pit1 Sodium-Dependent Phosphate Symporter,Pit1 Sodium-Phosphate Cotransporter,Pit2 Sodium-Dependent Phosphate Symporter,Pit2 Sodium-Phosphate Cotransporter,Ram-1 Receptor,SLC20A1 Transporter,Solute Carrier Family 20 (Phosphate Transporter), Member 1,Solute Carrier Family 20 (Phosphate Transporter), Member 2,Type III Na-Dependent Phosphate Cotransporter,Type III Sodium-Phosphate Symporter Proteins,Amphoteric Virus Receptor GLVR 2,Cotransporter, Pit1 Sodium-Phosphate,Cotransporter, Pit2 Sodium-Phosphate,GLVR 2 Receptor,MuLV Receptor, Amphotropic,Pit1 Sodium Dependent Phosphate Symporter,Pit1 Sodium Phosphate Cotransporter,Pit2 Sodium Dependent Phosphate Symporter,Pit2 Sodium Phosphate Cotransporter,Ram 1 Receptor,Receptor, Ram-1,Sodium Phosphate Cotransporter Proteins, Type III,Sodium-Phosphate Cotransporter, Pit1,Sodium-Phosphate Cotransporter, Pit2,Transporter Proteins, GLVR1,Type III Na Dependent Phosphate Cotransporter,Type III Sodium Phosphate Cotransporter Proteins,Type III Sodium Phosphate Symporter Proteins
D017989 Leukemia Virus, Gibbon Ape A species of GAMMARETROVIRUS causing leukemia in the gibbon ape. Natural transmission is by contact. Gibbon ape leukemia virus,GALV

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