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  • Cell-Based Therapy
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Cell-Based Therapy

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

Gene Therapy volume 7, pages 43–52 (2000)Cite this article

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.

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Acknowledgements

This work was supported by NIH grant AI-94012 to Judith M Thomas. We thank Clement Asiedu and Zhi Huang for their help with flow cytometry, and Arabella Tilden for her assistance with CD34+ processing and storage. Last but not least, Nat Borden took care of the rhesus animals with utmost ability.

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Authors and Affiliations

  1. Gene Therapy Center, Birmingham, AL, USA

    J Gómez-Navarro, W Arafat & D T Curiel

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

    J L Contreras, X L Jiang, B Hubbard & J M Thomas

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

    D Krisky, T Oligino, P Marconi & J C Glorioso

Authors
  1. J Gómez-Navarro
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  2. J L Contreras
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Gómez-Navarro, J., Contreras, J., Arafat, W. et al. Genetically modified CD34+ cells as cellular vehicles for gene delivery into areas of angiogenesis in a rhesus model. Gene Ther 7, 43–52 (2000). https://doi.org/10.1038/sj.gt.3301054

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