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- W2071570228 abstract "strategy is hampered by low efficiency of gene transfer and expression in repopulating HSC. To overcome this problem, we analyze the effect of overexpression of HoxB4, which can expand HSC, in mouse BM cells by transplantation of MLD mice. 5FU treated GFP mouse BM cells were transduced with retroviral vector expressing HoxB4 (B4) or control retroviral vector expressing GFP (MIG). After expansion of these transduced cells in vitro for five days transplantation was performed into irradiated MLD mice. High level of engraftment was observed in B4 transplanted MLD mice (B4MLD) compared to MIG transplanted MLD mice (MIGMLD)(92.4 vs. 36.5 %). ASA enzyme activity in serum was also increased in B4MLD compared to MIGMLD (19.8 vs. 10.3 nm/mg/hr). To evaluate the contribution of bone marrow cells as carriers for gene therapy of neurological disorders, we studied the fate of transplanted BM cells in the adult mouse brain. Efficient GFP positive neuronal cells were detected in B4MLD brain compared to MIGMLD brain. Immunohistochemical staining showed that most of the GFP positive cells ware IbaI positive microglia cells as we and others reported. In addition, O4 positive oligodendocyte like cells were identified only in the B4MLD brain but not in the MIGMLD brain (O4 positive/GFP positive: 6/326 vs. 0/312). This is the first demonstration indicating that systemically infused HSCc could differentiate to oligodendrocytes in adult mouse brain. It was recently suggested that HoxB4 could play a role in oligodendrocyte maturation. Our data strongly support that HSCs transduced with HoxB4 expression vector are useful for ex vivo gene therapy of CNS disorders as carriers of production of therapeutic protein and for regeneration of oligodendrocytes to treat demyelinating disorders such as MLD, Krabbe disease, and multiple sclerosis." @default.
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- W2071570228 date "2006-01-01" @default.
- W2071570228 modified "2023-09-25" @default.
- W2071570228 title "97. Translational Studies toward Optimizing In Vivo Bone Marrow Stem Cell Gene Transfer Using Lentiviral Vector" @default.
- W2071570228 doi "https://doi.org/10.1016/j.ymthe.2006.08.116" @default.
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