| Autor: |
Brenner S; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. Sebastian.Brenner@uniklinikum-dresden.de, Whiting-Theobald N, Kawai T, Linton GF, Rudikoff AG, Choi U, Ryser MF, Murphy PM, Sechler JM, Malech HL |
| Jazyk: |
angličtina |
| Zdroj: |
Stem cells (Dayton, Ohio) [Stem Cells] 2004; Vol. 22 (7), pp. 1128-33. |
| DOI: |
10.1634/stemcells.2003-0196 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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