ANGIOGENESIS-DIRECTED IMPLANTATION OF GENETICALLY-MODIFIED ENDOTHELIAL-CELLS IN MICE

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