Use of blood outgrowth endothelial cells as virus-producing vectors for gene delivery to tumors

Dragan Jevremovic, Rajiv Gulati, Ivo Hennig, Rosa Maria Diaz, Caroline Cole, Laurel Kleppe, Francois Loic Cosset, Robert D. Simari, Richard G. Vile

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Cell-based delivery of therapeutic viruses has potential advantages over systemic viral administration, including attenuated neutralization and improved viral targeting. One of the exciting new areas of investigation is the potential ability of endothelial-lineage cells to deliver genes to the areas of neovascularization. In the present study, we compared two types of endothelial-lineage cells [outgrowth endothelial cells (OECs) and culture-modified mononuclear cells (CMMCs), also known as "endothelial progenitor cells"] for their ability to be infected with adenovirus and to home to the areas of neovascularization. Both cell types were isolated from peripheral blood of healthy human donors and expanded in culture. We demonstrate that OECs are more infectable and home better to tumors expressing VEGF on systemic administration. Furthermore, we used an adenoviral/retroviral chimeric system to convert OECs to retrovirus-producing cells. When injected systemically into tumor-bearing mice, OECs retain their ability to produce retrovirus and infect surrounding tumor cells. Our data demonstrate that OECs could be efficient carriers for viral delivery to areas of tumor neovascularization.

Original languageEnglish (US)
Pages (from-to)H494-H500
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume287
Issue number2 56-2
DOIs
StatePublished - Aug 1 2004

Keywords

  • Cell carriers
  • Gene therapy
  • Stem cells
  • Viral vectors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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