Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration
Endothelial progenitor cell vascular endothelial growth factor gene transfer for vascular regeneration
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DOI：
10.1161/hc0602.103673
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发表时间：
2002-02-12
期刊：
影响因子：
37.8
通讯作者：
Asahara, T
中科院分区：
文献类型：
--
作者：
Iwaguro, H;Yamaguchi, J;Asahara, T
背景先前的研究已经证实，骨髓来源的内皮祖细胞（EPCs）存在于体循环中。在目前的研究中，我们研究了基因转移可以用来实现EPCs表型调节的假设。方法与结果：体外小鼠血管内皮生长因子（VEGF） 164基因转移增强了内皮细胞增殖活性，增强了内皮细胞在静止和活化的内皮细胞单层中的粘附和掺入。为了确定这种表型调节是否可能促进治疗性新生血管的形成，研究人员将编码VEGF的腺病毒转导的外源EPCs用于后肢缺血的胸腺裸小鼠；新生血管和血流恢复均得到改善，与对照组相比，肢体坏死/自动截肢减少了63.7%。体内实验中使用的内皮祖细胞剂量比之前的内皮祖细胞移植试验所需的剂量少30倍，以改善缺血肢体保留。接受dii标记的vegf转导的EPCs的动物尸检分析证实，体外证明增强的EPCs结合也有助于体内新生血管。结论体外。VEGF基因转移可促进EPC增殖。粘附，并融入内皮细胞单层。在体内，基因修饰的EPCs促进了细胞移植策略，以增强实验诱导肢体缺血动物模型中自然受损的新生血管。
Background-Previous studies have established that bone marrow-derived endothelial progenitor cells (EPCs) are present in the systemic circulation. In the current study, we investigated the hypothesis that gene transfer can be used to achieve phenotypic modulation of EPCs.Methods and Results-In vitro, ex vivo murine vascular endothelial growth factor (VEGF) 164 gene transfer augmented EPC proliferative activity and enhanced adhesion and incorporation of EPCs into quiescent as well as activated endothelial cell monolayers. To determine if such phenotypic modulation may facilitate therapeutic neovascularization, heterologous EPCs transduced with adenovirus encoding VEGF were administered to athymic nude mice with hindlimb ischemia; neovascularization and blood flow recovery were both improved, and limb necrosis/autoamputation were reduced by 63.7% in comparison with control animals. The dose of EPCs used for the in vivo experiments was 30 times less than that required in previous trials of EPC transplantation to improve ischemic limb salvage. Necropsy analysis of animals that received DiI-labeled VEGF-transduced EPCs confirmed that enhanced EPC incorporation demonstrated in vitro contributed to in vivo neovascularization as well.Conclusions-In vitro. VEGF EPC gene transfer enhances EPC proliferation. adhesion, and incorporation into endothelial cell monolayers. In vivo, gene-modified EPCs facilitate the strategy of cell transplantation to augment naturally impaired neovascularization in an animal model of experimentally induced limb ischemia.