Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets.
Vascular Repair by Circumferential Cell Therapy Using Magnetic Nanoparticles and Tailored Magnets.
复制标题
DOI：
10.1021/acsnano.5b04996
复制
发表时间：
2016-01
期刊：
影响因子：
17.1
通讯作者：
Sarah Vosen;S. Rieck;Alexandra Heidsieck;O. Mykhaylyk;Katrin Zimmermann;W. Bloch;D. Eberbeck;C. Plank;B. Gleich;A. Pfeifer;B. Fleischmann;D. Wenzel
中科院分区：
文献类型：
--
作者：
Sarah Vosen;S. Rieck;Alexandra Heidsieck;O. Mykhaylyk;Katrin Zimmermann;W. Bloch;D. Eberbeck;C. Plank;B. Gleich;A. Pfeifer;B. Fleischmann;D. Wenzel
心血管疾病通常是由内皮细胞（EC）功能障碍和动脉粥样硬化斑块在易发部位形成引起的。此外，清除斑块的外科手术也会对EC层造成不可逆的损伤，导致血管功能受损和再狭窄。在目前的研究中，我们研究了一种潜在的治疗方法，即在机械剥脱后对血管进行径向对称再内皮化。为此，将纳米技术与基因和细胞治疗相结合，应用于特定部位的再内皮化和血管功能恢复。我们使用慢病毒载体和磁性纳米颗粒（MNPs）复合物在内皮细胞中过表达血管保护基因内皮型一氧化氮合酶（eNOS）。负载mnp和过表达enos的细胞是磁性的，在磁场作用下，即使在流动条件下，它们也能以径向对称的方式定位在血管壁上。我们发现，处理后的血管显示出增强的eNOS表达和活性。此外，等长力测量显示，用eNOS过表达细胞替代EC可以恢复eNOS（-/-）小鼠体外和体内血管损伤后的内皮功能。因此，基于mnp的基因和细胞治疗与定制磁场的结合可以实现血管的周向再内皮化和血管功能的改善。
Cardiovascular disease is often caused by endothelial cell (EC) dysfunction and atherosclerotic plaque formation at predilection sites. Also surgical procedures of plaque removal cause irreversible damage to the EC layer, inducing impairment of vascular function and restenosis. In the current study we have examined a potentially curative approach by radially symmetric re-endothelialization of vessels after their mechanical denudation. For this purpose a combination of nanotechnology with gene and cell therapy was applied to site-specifically re-endothelialize and restore vascular function. We have used complexes of lentiviral vectors and magnetic nanoparticles (MNPs) to overexpress the vasoprotective gene endothelial nitric oxide synthase (eNOS) in ECs. The MNP-loaded and eNOS-overexpressing cells were magnetic, and by magnetic fields they could be positioned at the vascular wall in a radially symmetric fashion even under flow conditions. We demonstrate that the treated vessels displayed enhanced eNOS expression and activity. Moreover, isometric force measurements revealed that EC replacement with eNOS-overexpressing cells restored endothelial function after vascular injury in eNOS(-/-) mice ex and in vivo. Thus, the combination of MNP-based gene and cell therapy with custom-made magnetic fields enables circumferential re-endothelialization of vessels and improvement of vascular function.