Angiogenesis-directed Implantation of Genetically Modified Endothelial Cells in Mice1

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 incorpo rated into sites of active angiogenesis in vivo. To do so, we studied the fate of i.v.-injected, ¿acZ-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, ¿acZ-labeled human umbilical vein endothelial cells accumulated at sites of fibroblast growth factor-1-induced angiogen esis, 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.