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- Title
Sustained Long-Term Engraftment and Transgene Expression of Peripheral Blood CD34<sup>+</sup> Cells Transduced with Third-Generation Lentiviral Vectors.
- Authors
Tesio, Melania; Gammaitoni, Loretta; Gunetti, Monica; Leuci, Valeria; Pignochino, Ymera; Jordaney, Noela; Capellero, Sonia; Cammarata, Cristina; Caione, Luisa; Migliaretti, Giuseppe; Fagioli, Franca; Tabilio, Antonio; Aglietta, Massimo; Piacibello, Wanda
- Abstract
As mobilized peripheral blood (MPB) represents an attractive cell source for gene therapy, we investigated the ability of third-generation lentiviral vectors (LVs) to transfer the enhanced green fluorescent protein gene into MPB CD34+ cells in culture conditions allowing expansion of transplantable human hematopoietic stem cells. To date, few studies have reported transduction of MPB cells with vesicular stomatitis virus G pseudotyped LVs. The critical issue remains whether primitive, hematopoietic repopulating cells have, indeed, been transduced. In vitro (5 weeks' culture in FLT3 ligand + thrombopoietin + stem cell factor + interleukin 6) and in vivo (serial transplantation in NOD/SCID mice) experiments show that MPB CD34+ cells can be effectively long-term transduced by LV and maintain their proliferation, self-renewal, and multilineage differentiation potentials. We show that expansion following transduction improves the engraftment of transduced MPB CD34+ (4.6-fold expansion of SCID repopulating cells by limiting dilution studies). We propose ex vivo expansion after transduction as an effective tool to improve gene therapy protocols with MPB.
- Subjects
TRANSGENE expression; LENTIVIRUS diseases; HEMATOPOIETIC stem cells; GREEN fluorescent protein; STEM cells; BLOOD cells; BACTERIOPHAGES; GENETIC engineering
- Publication
Stem Cells, 2008, Vol 26, Issue 6, p1620
- ISSN
1066-5099
- Publication type
Article
- DOI
10.1634/stemcells.2008-0161