Magnetic Enhancement of Stem Cell-Targeted Delivery into the Brain Following MR-Guided Focused Ultrasound for Opening the Blood-Brain Barrier.
Magnetic Enhancement of Stem Cell-Targeted Delivery into the Brain Following MR-Guided Focused Ultrasound for Opening the Blood-Brain Barrier.
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DOI：
10.1177/0963689717715824
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发表时间：
2017-07
影响因子：
3.3
通讯作者：
Fishman PS
中科院分区：
文献类型：
--
作者：
Shen WB;Anastasiadis P;Nguyen B;Yarnell D;Yarowsky PJ;Frenkel V;Fishman PS
聚焦超声（FUS）介导的血脑屏障破坏（BBBD）甚至可以使干细胞等大型治疗药物从血流进入大脑。然而，效率相对较低。我们以前的研究表明，人类神经祖细胞（hNPC）加载超顺磁性氧化铁纳米粒子（SPION）在培养中被吸引的外部磁场。在体内，在创伤性脑损伤的大鼠模型中，在安装在颅骨上的磁体附近观察到增强的脑保留，其中BBBD也发生。本研究的目的是确定SPION负载的hNPC的磁吸引力是否也会在FUS介导的BBBD后增强其在脑中的保留。使用在1.5 MHz下操作的小动物磁共振成像（MRI）引导的FUS系统治疗大鼠（120 g），无组织损伤或出血。通过声处理后TI MRI上钆的放射学增强和伊文思蓝染料的全脑切片可视化来验证BBBD成功的证据。然后将该过程与静脉注射hNPC后直接向头部施加强力磁体相结合。通过用Perls普鲁士蓝对铁进行染色以及通过用人类特异性抗原进行免疫组织化学来进行脑内细胞的验证。通过注射相同数量的氧化铁（SPION）和非氧化铁纳米颗粒负载的hNPC，每个标记有不同的荧光团，我们发现显着更多的SPION负载的细胞保留在大脑中的BBBD的网站相比，noniron负载的细胞。这一结果在最靠近颅骨的大脑区域（背侧皮质）中最明显，靠近磁体表面。更强大的磁铁和Halbach磁性阵列导致SPION标记的细胞更有效地保留在更深的大脑区域，如纹状体和腹侧皮质。在那里，观察到的高达90%的hNPC含有SPION，相比之下，60%至70%的磁铁强度较低。与2 h相比，在处理后24 h观察到较少的细胞（主要在背侧皮质中）。这些结果表明，磁吸引可以大大提高FUS介导的BBBD后干细胞的保留。与直接颅内注射相比，这种方法可以提供一种更安全，侵入性更小的方法将干细胞输送到大脑，大大降低出血和感染的风险。
Focused ultrasound (FUS)-mediated blood–brain barrier disruption (BBBD) can enable even large therapeutics such as stem cells to enter the brain from the bloodstream. However, the efficiency is relatively low. Our previous study showed that human neural progenitor cells (hNPCs) loaded with superparamagnetic iron oxide nanoparticles (SPIONs) in culture were attracted by an external magnetic field. In vivo, enhanced brain retention was observed near a magnet mounted on the skull in a rat model of traumatic brain injury, where BBBD also occurs. The goal of the current study was to determine whether magnetic attraction of SPION-loaded hNPCs would also enhance their retention in the brain after FUS-mediated BBBD. A small animal magnetic resonance imaging (MRI)-guided FUS system operating at 1.5 MHz was used to treat rats (∼120 g) without tissue damage or hemorrhage. Evidence of successful BBBD was validated with both radiologic enhancement of gadolinium on postsonication TI MRI and whole brain section visualization of Evans blue dye. The procedure was then combined with the application of a powerful magnet to the head directly after intravenous injection of the hNPCs. Validation of cells within the brain was performed by staining with Perls’ Prussian blue for iron and by immunohistochemistry with a human-specific antigen. By injecting equal numbers of iron oxide (SPIONs) and noniron oxide nanoparticles–loaded hNPCs, each labeled with a different fluorophore, we found significantly greater numbers of SPIONs-loaded cells retained in the brain at the site of BBBD as compared to noniron loaded cells. This result was most pronounced in regions of the brain closest to the skull (dorsal cortex) in proximity to the magnet surface. A more powerful magnet and a Halbach magnetic array resulted in more effective retention of SPION-labeled cells in even deeper brain regions such as the striatum and ventral cortex. There, up to 90% of hNPCs observed contained SPIONs compared to 60% to 70% with the less powerful magnet. Fewer cells were observed at 24 h posttreatment compared to 2 h (primarily in the dorsal cortex). These results demonstrate that magnetic attraction can substantially enhance the retention of stem cells after FUS-mediated BBBD. This procedure could provide a safer and less invasive approach for delivering stem cells to the brain, compared to direct intracranial injections, substantially reducing the risk of bleeding and infection.
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影响因子：
2.9
作者：
Crake, Calum;Owen, Joshua;Stride, Eleanor
通讯作者：
Stride, Eleanor
影响因子：
11.3
作者：
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二氧化硅包覆的超顺磁性氧化铁纳米粒子靶向缺血性脑损伤中的 EPC
影响因子：
14
作者：
Li, Qianyun;Tang, Guanghui;Yang, Guo-Yuan
通讯作者：
Yang, Guo-Yuan
影响因子：
2.9
作者：
McDannold, Nathan;Vykhodtseva, Natalia;Hynynen, Kullervo
通讯作者：
Hynynen, Kullervo
影响因子：
3.5
作者：
McDannold, N;Vykhodtseva, N;Hynynen, K
通讯作者：
Hynynen, K