In vivo enhancement of angiogenesis by adenoviral transfer of HIF-1α-modified endothelial progenitor cells (Ad-HIF-1α-modified EPC for angiogenesis)
In vivo enhancement of angiogenesis by adenoviral transfer of HIF-1α-modified endothelial progenitor cells (Ad-HIF-1α-modified EPC for angiogenesis)
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DOI：
10.1016/j.biocel.2008.03.012
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Pu, Jun
中科院分区：
文献类型：
--
作者：
Jiang, Meng;Wang, Binyao;Pu, Jun
缺氧诱导因子（HIF）-1 α过表达可能在缺氧诱导的病理生理过程（如缺血性疾病）的细胞治疗中具有有益作用。我们先前的研究显示了通过HIF-1 α转染体外修饰内皮祖细胞（EPCs）的可行性。在这项研究中，我们试图确定这种离体修饰的EPCs是否促进功能性治疗性新血管形成。在体外将Ad-HIF-1 α转染人EPC。将HIF-1 α转导的EPCs给予后肢缺血的裸鼠。BrdU标记的这些EPCs表明，它们增强了体内的新血管形成。移植后第14天，HIF-1 α-EPC组肢体和足趾坏死较GFP-EPC组和培养基对照组明显减少（均P < 0.05）。直到随访1个月和2个月，在HIF-1 α组中仍然观察到统计学显著差异。通过组织学和生理学评估改善了新血管形成。观察到外源性EPC归巢。HIF-1 α过表达可促进缺血区HIF-1 α mRNA和蛋白的表达。通过检测HIF-1 α下游基因的表达，探讨EPC归巢的可能机制。总之，HIF-1 α-EPC基因转移增强了实验诱导的小鼠后肢缺血体内受损的新血管形成。(c)2008爱思唯尔有限公司保留所有权利。
Hypoxia inducible factor (HIF)-1 alpha over-expression may have beneficial effects in cell therapy of hypoxia-induced pathophysiological processes, such as ischemic disease. Our previous study showed the feasibility of ex vivo modification of endothelial progenitor cells (EPCs) by HIF-1 alpha transfection. In this study, we sought to determine if such ex vivo modified EPCs facilitated functional therapeutic neovascularization. Ad-HIF-1 alpha was transduced inhuman EPC in vitro. HIF-1 alpha-transduced EPCs were administered to nude mice with hind limb ischemia. BrdU-labeling of these EPCs showed that they enhanced neovascularization in vivo. Limb and toe necrosis was significantly reduced in HIF-1 alpha-EPC group compared to GFP-EPC group and medium control group at 14 days after transplantation (both P < 0.05). A statistically significant difference was still observed in the HIF-1 alpha group until 1 and 2 months of follow-up. Neovascularization was improved by both histological and physiological assessments. Exogenous EPC homing was observed. HIF-to over-expression enhanced its mRNA and protein expression in the ischemia zone. The expression of genes downstream of HIF-1 alpha was examined to explore the possible mechanism of EPC homing. In conclusion, HIF-1 alpha-EPC gene transfer augments impaired neovascularization in experimentally induced mouse hindlimb ischemia in vivo. (c) 2008 Elsevier Ltd. All rights reserved.