Magnetic Nanoparticle-Mediated Gene Transfer to Oligodendrocyte Precursor Cell Transplant Populations Is Enhanced by Magnetofection Strategies
Magnetic Nanoparticle-Mediated Gene Transfer to Oligodendrocyte Precursor Cell Transplant Populations Is Enhanced by Magnetofection Strategies
复制标题
DOI：
10.1021/nn2018717
复制
发表时间：
2011-08-01
期刊：
影响因子：
17.1
通讯作者：
Chari, Divya M.
中科院分区：
文献类型：
--
作者：
Jenkins, Stuart I.;Pickard, Mark R.;Chari, Divya M.
这项研究验证了使用物理方法的可行性。交付)方法，采用。静电场和振荡场“磁流控”技术，以增强磁性纳米颗粒介导的基因转移到用于移植治疗的大鼠少突胶质前体细胞。这些细胞是主要的移植群体，介导损伤的修复，如脊髓损伤和多发性硬化症等神经疾病。我们第一次展示了这种磁性。纳米颗粒介导报告基因和治疗基因的有效转移到少突胶质细胞前体细胞；施加静磁场或振荡磁场，后者使用使用高梯度NdFeB磁体的振荡阵列，显著提高了转染率。振荡场的影响是频率相关的，4赫兹产生最佳结果。利用磁染法获得的转染率与目前广泛使用的非病毒转染法(如电穿孔和脂质体)具有很高的竞争或更好的竞争能力，同时还具有高细胞存活率的关键优势。没有发现对细胞分裂或产生子代细胞的能力产生不利影响，少突胶质细胞是支撑其促进再生效果的关键属性。在以脑片为宿主组织的三维组织工程模型中，测试了转基因细胞的移植潜力；修改。移植的细胞被发现可以迁移、分裂、产生子代细胞，并整合到宿主组织中，进一步证明了所使用的方案的安全性。我们的发现有力地支持了这样一个概念，即磁性纳米颗粒载体与最先进的磁感应策略相结合，为将基因转移到少突胶质前体细胞提供了一种技术上简单而有效的替代方法。
This study has tested the feasibility of using physical. deliver) Methods, employing. static and oscillating field "magnetofection" techniques, to enhance magnetic nanoparticle-mediated gene transfer to rat oligodendrocyte precursor cells derived for transplantation therapies. These cells are a major transplant population to mediate repair of damage as occurs in spinal cord injury and neurological diseases such as multiple sclerosis. We show for the first time that magnetic. nanoparticles mediate effective transfer of reporter and therapeutic genes to oligodendrocyte precursors; transfection efficacy was significantly enhanced by applied static oroscillating magnetic fields, the latter using an oscillating array employing high-gradient NdFeB magnets. The effects of oscillating fields were frequency-dependent, with 4 Hz yielding optimal results. Transfection efficacies obtained using magnetofection methods were highly competitive with or better than current-widely used nonviral transfectlon methods (e.g., electroporation and lipofection) with the additional critical advantage of high cell viability. No adverse effects Were found on the cells' ability to divide or give rise to their daughter cells, the oligodendrocytes-key properties that underpin their regeneration-promoting effects. The transplantation potential of transfected cells was tested, in three-dimensional tissue engineering models utilizing brain slices as the host tissue; modified. transplanted cells were found to migrate, divide, give rise to daughter cells, and integrate within host tissue, further evidencing the safety of the protocols used. Our findings strongly support the concept that magnetic nanoparticle vectors In conjunction with state-of-the-art magnetofection strategies provide a technically simple and effective alternative to current methods for gene transfer to oligodendrocyte precursor cells.