Bone marrow-derived, endothelial progenitor-like cells as angiogenesis-selective gene-targeting vectors

被引:70
作者
Ferrari, N [1 ]
Glod, J [1 ]
Lee, J [1 ]
Kobiler, D [1 ]
Fine, HA [1 ]
机构
[1] NINDS, Neurooncol Branc, NCI, NIH, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
bone marrow; endothelial progenitor; cancer therapy; anti-angiogenesis; TUMOR ANGIOGENESIS; CD34(+) CELLS; STEM-CELLS; GROWTH; TRANSDUCTION; PRECURSORS; EXPRESSION; RETROVIRUS; PROTEINS; ORIGIN;
D O I
10.1038/sj.gt.3301883
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human and mouse proliferation-competent, bone marrow or peripheral circulation derived endothelial progenitor-like cells (EPCs) were isolated, expanded and genetically engineered ex vivo to express the beta galactosidase (beta-gal), green fluorescence protein or thymidine kinase (TK) genes using retrovirus-mediated gene transfer. Genetically labeled EPCs were transplanted into sublethally irradiated tumor-bearing mice and were found to migrate to and incorporate into the angiogenic vasculature of growing tumors while maintaining transgene expression. Ganciclovir treatment resulted in significant tumor necrosis in animals previously administered TK-expressing EPCs with no systemic toxicity. These results demonstrate the feasibility of using genetically modified EPCs as angiogenesis-selective gene-targeting vectors and the potential of this approach to mediate non-toxic and systemic antitumor responses.
引用
收藏
页码:647 / 656
页数:10
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