Abstract:
:In previous studies we showed that 5 days of treatment with granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) mobilized murine repopulating cells to the peripheral blood (PB) and that these cells could be efficiently transduced with retroviral vectors. We also found that, 7-14 days after cytokine treatment, the repopulating ability of murine bone marrow (BM) increased 10-fold. In this study we examined the efficiency of gene transfer into cytokine-primed murine BM cells and extended our observations to a nonhuman primate autologous transplantation model. G-CSF/SCF-primed murine BM cells collected 7-14 days after cytokine treatment were equivalent to post-5-fluorouracil BM or G-CSF/SCF-mobilized PB cells as targets for retroviral gene transfer. In nonhuman primates, CD34-enriched PB cells collected after 5 days of G-CSF/SCF treatment and CD34-enriched BM cells collected 14 days later were superior targets for retroviral gene transfer. When a clinically approved supernatant infection protocol with low-titer vector preparations was used, monkeys had up to 5% of circulating cells containing the vector for up to a year after transplantation. This relatively high level of gene transfer was confirmed by Southern blot analysis. Engraftment after transplantation using primed BM cells was more rapid than that using steady-state bone marrow, and the fraction of BM cells saving the most primitive CD34+/CD38- or CD34+/CD38dim phenotype increased 3-fold. We conclude that cytokine priming with G-CSF/SCF may allow collection of increased numbers of primitive cells from both the PB and BM that have improved susceptibility to retroviral transduction, with many potential applications in hematopoietic stem cell-directed gene therapy.
journal_name
Proc Natl Acad Sci U S Aauthors
Dunbar CE,Seidel NE,Doren S,Sellers S,Cline AP,Metzger ME,Agricola BA,Donahue RE,Bodine DMdoi
10.1073/pnas.93.21.11871subject
Has Abstractpub_date
1996-10-15 00:00:00pages
11871-6issue
21eissn
0027-8424issn
1091-6490journal_volume
93pub_type
杂志文章abstract::The Ten-Eleven-Translocation 2 (TET2) gene encodes a member of TET family enzymes that alters the epigenetic status of DNA by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Somatic loss-of-function mutations of TET2 are frequently observed in patients with diverse myeloid malignancies, including myelody...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1112317108
更新日期:2011-08-30 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0602012103
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abstract::Wnt signaling is required for the maintenance of intestinal stem cells and self-renewal of the intestinal epithelium. Intestinal cancers are frequently associated with mutations that activate the Wnt pathway. The role of Wnt signaling on differentiation of lineage-specific precursors in the intestine is not well chara...
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doi:10.1073/pnas.0702665104
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.1.106
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.87.20.8125
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.212408299
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2000-01-04 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.12.5306
更新日期:1992-06-15 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.8.4438
更新日期:1999-04-13 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.79.2.476
更新日期:1982-01-01 00:00:00
abstract::The self assembly of phospholipid molecules in the bilayer form was considered in terms of equivalent molecular shapes representing intermolecular forces. The equivalent size of each phospholipid headgroup was approximated by the net atomic volume plus the volume of the associated water molecules, which was derived fr...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.86.15.5825
更新日期:1989-08-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2013-10-29 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2010-12-14 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1985-12-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1978-03-01 00:00:00
abstract::To elucidate the molecular mechanism of frameshift suppression by the SUF2 gene of yeast, the sequences of DNA fragments carrying the SUF2-1 and suf2+ alleles of the gene and surrounding regions have been determined. Comparison of the suppressor and wild-type sequences indicates that the SUF2 gene product is a proline...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1982-06-01 00:00:00
abstract::Two NADPH:cytochrome P450 oxidoreductases (CPRs) from parsley (Petroselinum crispum) were cloned, and the complete proteins were expressed and functionally identified in yeast. The two enzymes, designated CPR1 and CPR2, are 80% identical in amino acid sequence with one another and about 75% identical with CPRs from se...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1997-12-23 00:00:00
abstract::The one-sided multipliers of an operator space X are a key to "latent operator algebraic structure" in X. We begin with a survey of these multipliers, together with several of the applications that they have had to operator algebras. We then describe several new results on one-sided multipliers, and new applications, ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2004-01-20 00:00:00
abstract::Previously we reported that pretreatment of rats with the substance P (SP) antagonist CP-96,345 inhibits the enterotoxic responses following administration of toxin A from Clostridium difficile into ileal loops, indicating that SP participates in the intestinal responses to this toxin. We now report that injection of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.9.4788
更新日期:1997-04-29 00:00:00