Comparison of Viral and Nonviral Vectors for Gene Transfer to Human Endothelial Progenitor Cells

被引:15
|
作者
Kealy, Brian
Liew, Aaron
McMahon, Jill M.
Ritter, Thomas
O'Doherty, Aideen
Hoare, Melissa
Greiser, Udo
Vaughan, Erin E.
Maenz, Martin
O'Shea, Ciara
Barry, Frank
O'Brien, Timothy [1 ]
机构
[1] Natl Univ Ireland, Regenerat Med Inst, Natl Ctr Biomed Engn Sci, Galway, Ireland
基金
爱尔兰科学基金会;
关键词
TRANSGENE EXPRESSION; STEM-CELLS; HEMATOPOIETIC PROGENITOR; HEMOPHILIA-A; THERAPY; TRANSPLANTATION; PURIFICATION; TITER; ELECTROPORATION; RECEPTOR;
D O I
10.1089/ten.tec.2008.0323
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Background/Aims: The ability of endothelial progenitor cells (EPCs) to home to sites of neoangiogenesis makes them attractive candidates for use in the field of gene therapy. The efficacy of this approach depends on the efficiency of the vector used for transgene delivery. Methods/Results: In this study, we have compared the efficiency of adenovirus, five serotypes of AAV2, VSVG-pseudotyped lentivirus, and nonviral plasmid/liposome DNA vectors to deliver the green fluorescence protein reporter gene to human early EPCs to determine efficacy and vector-related cell toxicity. Adenovirus proved most effective with efficiencies of up to 80% with low levels of cell death. Lower levels of expression were seen with other vectors. Electroporation proved unsuitable at the parameters tested. We have also identified at least two distinct subpopulations that exist in the heterogeneous parent EPC culture, one of which is amenable to transduction with adenovirus and one that is not. In addition, adenoviral transduction did not disrupt the ability of the cells to incorporate into endothelial structures in vitro. Conclusion: We have found adenovirus to be the most efficient of the vector systems tested for gene delivery to EPCs, an effect that is mediated almost entirely by one of two identified subpopulations.
引用
收藏
页码:223 / 231
页数:9
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