This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ojeifo, J. O. Articles by Zwiebel, J. A. Search for Related Content PubMed PubMed Citation Articles by Ojeifo, J. O. Articles by Zwiebel, J. A.

Angiogenesis-directed Implantation of Genetically Modified Endothelial Cells in Mice¹

Department of Medicine, Division of Hematology and Oncology [J. O. O., S. P., J. A. Z.], Department of Pathology [J. A. Z.], and the Vincent T. Lombardi Cancer Research Center [J. O. O., S. P., J. A. Z.], Georgetown University Medical Center, Washington, DC 20007, and Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855 [R. F., T. M.]

By virtue of their location within blood vessels and their ability to express foreign genes, endothelial cells are attractive vehicles for the delivery of therapeutic molecules in vivo. We wished to determine whether i.v.-injected, genetically modified endothelial cells can become incorporated into sites of active angiogenesis in vivo. To do so, we studied the fate of i.v.-injected, lacZ-expressing human umbilical vein endothelial cells in athymic nude mice bearing lethally irradiated NIH 3T3 murine fibroblast cells transfected with a sp-hst/KS3:fibroblast growth factor-1 chimera that forces the secretion of the angiogenic protein, fibroblast growth factor-1. Following i.v. injection, lacZ-labeled human umbilical vein endothelial cells accumulated at sites of fibroblast growth factor-1-induced angiogenesis, persisting for at least 4 weeks. These results suggest that i.v.-administered, genetically modified endothelial cells can migrate into and survive within an angiogenic site. This strategy may be useful for delivery of therapeutic molecules to sites of pathological angiogenesis during tumor metastasis.

¹ Supported in part by NIH Grants HL32348 and HL44336 (to T. M.) and by NIH Grants HL48334 and CA59311 (to J. A. Z.). A preliminary report was presented at the American Society of Hematology, December, 1992.

² Present address: Department of Surgery, University of Washington, Seattle, WA 98195.

³ To whom requests for reprints should be addressed, at Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007.

Received 2/24/95. Accepted 4/24/95.

This article has been cited by other articles:

				D. G. Duda Endothelial cell-based therapy for hematopoiesis Blood, March 15, 2007; 109(6): 2272 - 2273. [Full Text] [PDF]

				F. A. Scappaticci Mechanisms and Future Directions for Angiogenesis-Based Cancer Therapies J. Clin. Oncol., September 15, 2002; 20(18): 3906 - 3927. [Abstract] [Full Text] [PDF]

				J. Ma, K. A. Reed, and J. M. Gallo Cells Designed to Deliver Anticancer Drugs by Apoptosis Cancer Res., March 1, 2002; 62(5): 1382 - 1387. [Abstract] [Full Text] [PDF]

				E.-J. Kim, R.-K. Li, R. D. Weisel, D. A.G. Mickle, Z.-Q. Jia, S. Tomita, T. Sakai, and T. M. Yau Angiogenesis by endothelial cell transplantation J. Thorac. Cardiovasc. Surg., November 1, 2001; 122(5): 963 - 971. [Abstract] [Full Text] [PDF]

				W. O. Arafat, E. Casado, M. Wang, R. D. Alvarez, G. P. Siegal, J. C. Glorioso, D. T. Curiel, and J. Gomez-Navarro Genetically Modified CD34+ Cells Exert a Cytotoxic Bystander Effect on Human Endothelial and Cancer Cells Clin. Cancer Res., November 1, 2000; 6(11): 4442 - 4448. [Abstract] [Full Text] [PDF]

				A. Hatzopoulos, J Folkman, E Vasile, G. Eiselen, and R. Rosenberg Isolation and characterization of endothelial progenitor cells from mouse embryos Development, January 4, 1998; 125(8): 1457 - 1468. [Abstract] [PDF]