期刊
STEM CELLS
卷 22, 期 7, 页码 1128-1133出版社
ALPHAMED PRESS
DOI: 10.1634/stemcells.2003-0196
关键词
engraftment; CXCR4; ex vivo gene transfer; hematopoietic stem cells (HSCs)
资金
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [Z01AI000615, Z01AI000644, Z01AI000645, ZIAAI000644, ZIAAI000615, ZIAAI000645] Funding Source: NIH RePORTER
Hematopoietic stem cells (HSCs) lose marrow reconstitution potential during ex vivo culture. HSC migration to stromal cell-derived factor (SDF)-1 (CXCL12) correlates with CXC chemokine receptor 4 (CXCR4) expression and marrow engraftment. We demonstrate that mobilized human CD34(+) peripheral blood stem cells (CD34(+) PBSCs) lose CXCR4 expression during prolonged culture. We transduced CD34(+) PBSCs with retrovirus vector encoding human CXCR4 and achieved 18-fold more CXCR4 expression in over 87% of CD34(+) cells. CXCR4-transduced cells yielded increased calcium flux and up to a 10-fold increase in migration to SDF-1. Six-day cultured CXCR4-transduced cells demonstrated significant engraftment in nonobese diabetic/severe combined immunodeficient mice under conditions in which control transduced cells resulted in low or no engraftment. We conclude that transduction-mediated overexpression of CXCR4 significantly improves marrow engraftment of cultured PBSCs.
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