Genetically modified CD34+ cells as cellular vehicles for gene delivery into areas of angiogenesis in a rhesus model.
To develop a cellular vehicle able to reach systemically disseminated areas of angiogenesis, we sought to exploit the natural tropism of circulating endothelial progenitor cells (EPCs). Primate CD34+ EPCs were genetically modified with high efficiency and minimal toxicity using a non-replicative herpes virus vector. These EPCs localized in a skin autograft model of angiogenesis in rhesus monkeys, and sustained the expression of a reporter gene for several weeks while circulating in the blood. In animals infused with autologous CD34+ EPCs transduced with a thymidine kinase-encoding herpes virus, skin autografts and subcutaneous Matrigel pellets impregnated with vascular growth factors underwent necrosis or accelerated regression after administration of ganciclovir. Importantly, the whole intervention was perfectly well tolerated. The accessibility, easy manipulation, lack of immunogenicity of the autologous CD34+ cell vehicles, and tropism for areas of angiogenesis render autologous CD34+ circulating endothelial progenitors as ideal candidates for exploration of their use as cellular vehicles when systemic gene delivery to those areas is required. Gene Therapy (2000) 7, 43-52.
Gómez-Navarro
J
J
Gene Therapy Center, Birmingham, AL, USA.
Contreras
J L
JL
Arafat
W
W
Jiang
X L
XL
Krisky
D
D
Oligino
T
T
Marconi
P
P
Hubbard
B
B
Glorioso
J C
JC
Curiel
D T
DT
Thomas
J M
JM
D020533:Angiogenesis Inhibitors / Q000235:genetics; D000818:Animals; D018952:Antigens, CD34 / Q000235:genetics*; D002478:Cells, Cultured; D005434:Flow Cytometry; D018014:Gene Transfer Techniques; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008253:Macaca mulatta; D009389:Neovascularization, Pathologic; D018139:Simplexvirus / Q000235:genetics; D012867:Skin / Q000098:blood supply; D013234:Stem Cells / Q000502:physiology; D014161:Transduction, Genetic / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D018952:Antigens, CD34; D001616:beta-Galactosidase