首页> 外文期刊>American Journal of Physiology >Use of blood outgrowth endothelial cells as virus-producing vectors for gene delivery to tumors.
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Use of blood outgrowth endothelial cells as virus-producing vectors for gene delivery to tumors.

机译:血液增生内皮细胞作为产生病毒的载体用于基因传递至肿瘤的用途。

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摘要

Cell-based delivery of therapeutic viruses has potential advantages over systemic viral administration, including attenuated neutralization and improved viral targeting. One of the exciting new areas of investigation is the potential ability of endothelial-lineage cells to deliver genes to the areas of neovascularization. In the present study, we compared two types of endothelial-lineage cells [outgrowth endothelial cells (OECs) and culture-modified mononuclear cells (CMMCs), also known as "endothelial progenitor cells"] for their ability to be infected with adenovirus and to home to the areas of neovascularization. Both cell types were isolated from peripheral blood of healthy human donors and expanded in culture. We demonstrate that OECs are more infectable and home better to tumors expressing VEGF on systemic administration. Furthermore, we used an adenoviral/retroviral chimeric system to convert OECs to retrovirus-producing cells. When injected systemically into tumor-bearing mice, OECs retain their ability to produce retrovirus and infect surrounding tumor cells. Our data demonstrate that OECs could be efficient carriers for viral delivery to areas of tumor neovascularization.
机译:基于细胞的治疗性病毒传递相对于全身性病毒给药具有潜在的优势,包括减弱的中和作用和改进的病毒靶向性。令人兴奋的新研究领域之一是内皮谱系细胞将基因传递到新血管形成领域的潜在能力。在本研究中,我们比较了两种内皮谱系细胞[生长内皮细胞(OEC)和培养物修饰的单核细胞(CMMC),也称为“内皮祖细胞”]对腺病毒的感染和感染的能力。新血管形成领域的所在地。两种细胞类型均从健康人类供体的外周血中分离出来,并在培养中扩增。我们证明OECs更具感染性,并且在全身性给药时对表达VEGF的肿瘤的适应性更好。此外,我们使用腺病毒/逆转录病毒嵌合系统将OEC转换为产生逆转录病毒的细胞。当全身注射到荷瘤小鼠中时,OECs保留了产生逆转录病毒并感染周围肿瘤细胞的能力。我们的数据表明,OEC可能是有效的载体,可将病毒输送到肿瘤新血管形成区域。

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