Comparison of viral and nonviral vectors for gene transfer to human endothelial progenitor cells.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Kealy
Brian
B
Regenerative Medicine Institute, National Centre for Biomedical Engineering Science & Department of Medicine, National University of Ireland, Galway, Republic of Ireland.
Liew
Aaron
A
McMahon
Jill M
JM
Ritter
Thomas
T
O'Doherty
Aideen
A
Hoare
Melissa
M
Greiser
Udo
U
Vaughan
Erin E
EE
Maenz
Martin
M
O'Shea
Ciara
C
Barry
Frank
F
O'Brien
Timothy
T
D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D004338:Drug Combinations; D018274:Electroporation; D042783:Endothelial Cells / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D008081:Liposomes / Q000378:metabolism; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010957:Plasmids / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013194:Staining and Labeling; D013234:Stem Cells / Q000378:metabolism*; D014161:Transduction, Genetic; D014780:Viruses / Q000235:genetics*
D004338:Drug Combinations; D007797:Laminin; D008081:Liposomes; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D004247:DNA