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Am J Physiol Heart Circ Physiol 287: H494-H500, 2004; doi:10.1152/ajpheart.00064.2004
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Cellular Plasticity in the Cardiovascular System

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

Dragan Jevremovic,1,2 Rajiv Gulati,1,3 Ivo Hennig,1 Rosa Maria Diaz,1 Caroline Cole,1,4 Laurel Kleppe,1,3 Francois Loic Cosset,5 Robert D. Simari,1,3 and Richard G. Vile1,4

1Molecular Medicine Program, 2Division of Pathology, 3Division of Cardiovascular Diseases, and 4Division of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905; and 5Vectorologie Rétrovirale et Thérapie Génique, Institut National de la Santé et de la Recherche Médicale U412, Lyon Cedex 07, France

Submitted 30 March 2004 ; accepted in final form 30 March 2004

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.

stem cells; gene therapy; viral vectors; cell carriers


Address for reprint requests and other correspondence: R. G. Vile, Mayo Clinic, 18 Gugg, 200 First St. SW, Rochester, MN 55905 (E-mail: vile.richard{at}mayo.edu).




This article has been cited by other articles:


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S. Komarova, Y. Kawakami, M. A. Stoff-Khalili, D. T. Curiel, and L. Pereboeva
Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses.
Mol. Cancer Ther., March 1, 2006; 5(3): 755 - 766.
[Abstract] [Full Text] [PDF]


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