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Titolo:
Avoidance of stimulation improves engraftment of cultured and retrovirallytransduced hematopoietic cells in primates
Autore:
Takatoku, M; Sellers, S; Agricola, BA; Metzger, ME; Kato, I; Donahue, RE; Dunbar, CE;
Indirizzi:
NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA NHLBI Bethesda MD USA 20892 , Hematol Branch, NIH, Bethesda, MD 20892 USA Takara Shuzo Co, Biotechnol Res Labs, Otsu, Shiga, Japan Takara Shuzo Co Otsu Shiga Japan Biotechnol Res Labs, Otsu, Shiga, Japan
Titolo Testata:
JOURNAL OF CLINICAL INVESTIGATION
fascicolo: 3, volume: 108, anno: 2001,
pagine: 447 - 455
SICI:
0021-9738(200108)108:3<447:AOSIEO>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
EX-VIVO EXPANSION; BLOOD CD34(+) CELLS; GREEN FLUORESCENT PROTEIN; LONG-TERM ENGRAFTMENT; GROWTH-FACTOR-BETA; BONE-MARROW CELLS; STEM-CELLS; PERIPHERAL-BLOOD; PROGENITOR CELLS; GENE-TRANSFER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Dunbar, CE NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA NHLBI Bldg 10,Room 7C103,9000 Rockville Pike Bethesda MD USA 20892
Citazione:
M. Takatoku et al., "Avoidance of stimulation improves engraftment of cultured and retrovirallytransduced hematopoietic cells in primates", J CLIN INV, 108(3), 2001, pp. 447-455

Abstract

Recent reports suggest that cells in active cell cycle have an engraftmentdefect compared with quiescent cells. We used nonhuman primates to investigate this finding, which has direct implications for clinical transplantation and gene therapy applications. Transfer of rhesus CD34(+) cells to culture in stem cell factor (SCF) on the CH-296 fibronectin fragment (FN) after 4 days of culture in stimulatory cytokines maintained cell viability but decreased cycling. Using retroviral marking with two different gene transfer vectors, we compared the engraftment potential of cytokine-stimulated cellsversus those transferred to nonstimulatory conditions (SCF on FN alone) before reinfusion. In vivo competitive repopulation studies showed that the level of marking originating from the cells continued in culture for 2 days with SCF on FN following a 4-day stimulatory transduction was significantlyhigher than the level of marking coming from cells transduced for 4 days and reinfused without the 2-day culture under nonstimulatory conditions. We observed stable in vivo overall gene marking levels of up to 29%. This approach may allow more efficient engraftment of transduced or ex vivo expandedcells by avoiding active cell cycling at the time of reinfusion.

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Documento generato il 31/03/20 alle ore 19:35:45