1. Direct comparison of steady-state marrow, primed marrow, and mobilized peripheral blood for transduction of hematopoietic stem cells in dogs.
- Author
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Thomasson B, Peterson L, Thompson J, Goerner M, and Kiem HP
- Subjects
- Animals, Antigens, CD34 biosynthesis, Bone Marrow Cells cytology, Dogs, Gene Transfer Techniques, Granulocyte Colony-Stimulating Factor metabolism, Growth Substances metabolism, Hematopoiesis, Hematopoietic Stem Cell Transplantation, Polymerase Chain Reaction, Retroviridae genetics, Stem Cell Factor metabolism, Time Factors, Bone Marrow pathology, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cells cytology, Stem Cell Transplantation
- Abstract
The optimal stem cell source for stem cell gene therapy has not been defined. Most gene transfer studies have used peripheral blood or marrow repopulating cells collected after administration of granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF). For clinical applications, however, growth factor administration may not be feasible. Thus, in the current study we used a competitive repopulation assay in the dog to directly compare transduction efficiency of steady-state marrow, G-CSF/SCF-primed marrow, and G-CSF/SCF-mobilized peripheral blood. Cells from all three sources were transduced, cryopreserved, and thawed together before infusion into myeloablated dogs. Gene marking in hematopoietic repopulating cells was assessed by polymerase chain reaction. While primed marrow resulted in the highest long-term marking levels, steady-state marrow was transduced at least as efficiently as mobilized peripheral blood in all three dogs. These results suggest that steady-state marrow may be an appropriate source for genetic modification of hematopoietic stem cells.
- Published
- 2003
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