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- Title
SDF-1a/CXCL12 enhances retroviral-mediated gene transfer into immature subsets of human and murine hematopoietic progenitor cells.
- Authors
Tao, W.; Hangoc, G.; Cooper, S.; Broxmeyer, H.E.
- Abstract
Genetic modification of hematopoietic stem and progenitor cells has the potential to treat diseases affecting blood cells. Oncoretroviral vectors have been used for gene therapy; however, clinical success has been limited in part by low gene transfer efficiencies. We found that the presence of stromal-derived factor 1 (SDF-1a)/CXCL12 during retroviral transduction significantly enhanced, in a dose-dependent fashion, gene transfer into immature subsets of high proliferative human and murine hematopoietic progenitor cells. Murine mononuclear bone marrow cells and purified c-Kit+Lin- bone marrow cells were prestimulated and transduced with the bicistronic retroviral vector MIEG3 on Retronectin-coated surfaces in the presence and absence of SDF-1. SDF-1 enhanced gene transduction of murine bone marrow and c-Kit+Lin- cells by 35 and 29%, respectively. Moreover, SDF-1 enhanced transduction of progenitors in these populations by 121 and 107%, respectively. SDF-1 also enhanced transduction of human immature subsets of high proliferative progenitors present in either nonadherent mononuclear or CD34+ umbilical cord blood cells. Transduction of hematopoietic progenitors was further increased by preloading Retronectin-coated plates with retrovirus using low-speed centrifugation followed by increasing cell-virus interactions through brief centrifugation during the transduction procedure. These results may be of clinical relevance.Gene Therapy (2004) 11, 61-69. doi:10.1038/sj.gt.3302127
- Subjects
GENETIC transduction; GENETIC transformation; HEMATOPOIETIC stem cells; HEMATOPOIESIS; RETROVIRUSES; GENETICS
- Publication
Gene Therapy, 2004, Vol 11, Issue 1, p61
- ISSN
0969-7128
- Publication type
Article
- DOI
10.1038/sj.gt.3302127