Granulocyte Colony-Stimulating Factor Prior To Low-Dose Total Body Irradiation As Conditioning Regimen In Hematopoietic Stem Cell Transplantation For Gene Therapy.
BLOOD(2004)
摘要
Genetic blood diseases can potentially be treated by transplantation of autologous hematopoietic stem cells (HSC) transduced with the functional gene. Nonmyeloablative conditioning regimens such as low-dose total body irradiation (LDTBI) can enhance competitive engraftment in the absence of a selective advantage for HSC. Granulocyte colony-stimulating factor (G-CSF) treatment of recipients prior to LDTBI has been shown to enhance engraftment of fresh bone marrow (BM) cells, but the underlying mechanisms and whether this combined approach can enhance long-term engraftment of genetically transduced donor cells have not been defined. We examined whether pre-treatment of recipient mice with G-CSF prior to LDTBI improves long-term donor engraftment of retroviral vector-transduced HSC in murine X-linked chronic granulomatous disease (X-CGD). In initial studies, we verified that pre-treatment of wild type mice with 4 ug G-CSF SC BID for 5 days prior to irradiation with either 160 cGy or 300 cGy significantly increased long-term engraftment of congenic fresh BM cells (see Table).
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关键词
hematopoietic stem cell transplantation,gene therapy,total body irradiation,stem cell,colony-stimulating,low-dose
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