Angiogenesis-directed implantation of genetically modified endothelial cells in mice.
Angiogenesis-directed implantation of genetically modified endothelial cells in mice.
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DOI：
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发表时间：
1995-06
期刊：
影响因子：
11.2
通讯作者：
J. Ojeifo;R. Forough;S. Paik;T. Maciag;J. Zwiebel
中科院分区：
文献类型：
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作者：
J. Ojeifo;R. Forough;S. Paik;T. Maciag;J. Zwiebel
由于其在血管内的位置和表达外源基因的能力，内皮细胞是体内输送治疗分子的有吸引力的载体。我们希望确定静脉注射的转基因内皮细胞是否可以在体内整合到活跃的血管生成部位。为此，我们研究了静脉注射表达LacZ的人脐静脉内皮细胞在裸鼠体内的命运，该裸鼠携带致死照射的NIH3T3小鼠成纤维细胞，该细胞转染了SP-hst/KS3：成纤维细胞生长因子-1嵌合体，该嵌合体迫使血管生成蛋白成纤维细胞生长因子-1的分泌。跟随静脉注射。注射后，LacZ标记的人脐静脉内皮细胞聚集在成纤维细胞生长因子-1诱导的血管生成部位，持续至少4周。这些结果表明，静脉注射的转基因内皮细胞可以迁移到血管生成部位并在其中存活。这一策略可能有助于在肿瘤转移过程中将治疗分子输送到病理性血管生成的部位。
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.