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Gene Therapy
January 2000, Volume 7, Issue 1, Pages 43 – 52
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Title

Genetically modified CD34+ cells as cellular vehicles for gene delivery into areas of angiogenesis in a rhesus model

J Gómez-Navarro1, JL Contreras2, W Arafat1, XL Jiang2, D Krisky3, T Oligino3, P Marconi3, B Hubbard2, JC Glorioso3, DT Curiel1 & JM Thomas2

1Gene Therapy Center, Birmingham, AL, USA

2Transplant Immunobiology, Department of Surgery, Birmingham, AL, USA

3Department of Molecular Genetics and Biochemistry, E1240 Biomedical Science Tower, Pittsburgh, PA 15261, USA

Correspondence to: JM Thomas, Transplant Immunobiology, Department of Surgery, 1808 Seventh Avenue South, BDB 563, Birmingham, AL 35294, USA


Abstract

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.

Keywords
rhesus monkey; CD34 cell; gene transfer; herpes simplex virus; herpes simplex virus thymidine kinase; anti-angiogenesis


Received 19 July 1999; Accepted 9 August 1999


© Macmillan Publishers Ltd 2000