使用钕磁铁靶向递送铁氧化物标记的人神经干细胞在大鼠局灶性脑缺血模型中。

Using a neodymium magnet to target delivery of ferumoxide-labeled human neural stem cells in a rat model of focal cerebral ischemia.

机构信息

Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, South Korea.

出版信息

Hum Gene Ther. 2010 May;21(5):603-10. doi: 10.1089/hum.2009.144.

Abstract

Efficiency of targeted delivery of stem cells via transplantation by intravenous injection is limited because of rapid clearance. Thus, more effective, newer methods are required. We hypothesized that combining the use of ferumoxide labeling and magnetic fields could enhance targeted delivery of stem cells. The effects of a magnetic field on proliferation, viability, and differentiation of human neural stem cells (NSCs) were determined in culture, and the results indicated that the difference between control and cultures exposed to a magnetic field were insignificant. To assess migration in vitro, ferumoxide-labeled cells were seeded into a culture dish that had a neodymium magnet below its center, and the labeled NSCs were found to aggregate above the magnet. To investigate targeted delivery of NSCs in vivo, rats were separated into three groups: ischemia only (IO), ischemia with injection of ferumoxide-labeled cells (IC), and ischemia with injection of labeled cells and magnet exposure (ICM). Twenty-four hours after middle cerebral artery occlusion (MCAo), labeled human NSCs were injected into the tail vein. Seven days after MCAo, ICM rats had a larger number and greater distribution of Prussian blue-positive NSCs as compared with controls. In addition, infarct volume in ICM rats was significantly reduced. Our study suggests that this use of a magnetic field may be useful for improving the efficacy of targeted migration of stem cells in stem-based cell therapy in ischemic brain injury.

摘要

通过静脉注射移植将干细胞靶向递送至体内的效率受到快速清除的限制。因此,需要更有效、更新的方法。我们假设,结合使用超顺磁氧化铁(ferumoxide)标记和磁场可以增强干细胞的靶向递送。我们在培养中确定了磁场对人神经干细胞(NSC)增殖、活力和分化的影响,结果表明,暴露于磁场的培养物与对照组之间的差异不显著。为了评估体外迁移,将铁氧体标记的细胞播种到培养皿中,培养皿的中心下方有一块钕磁铁,结果发现标记的 NSCs 在磁铁上方聚集。为了研究体内 NSCs 的靶向递送,将大鼠分为三组:仅缺血(IO)、缺血加铁氧体标记细胞注射(IC)和缺血加标记细胞注射和磁场暴露(ICM)。大脑中动脉闭塞(MCAo)后 24 小时,将标记的人 NSCs 尾静脉注射。MCAo 后 7 天,与对照组相比,ICM 大鼠的普鲁士蓝阳性 NSCs 数量更多,分布更广。此外,ICM 大鼠的梗死体积明显减少。我们的研究表明,这种磁场的使用可能有助于提高基于干细胞的细胞治疗中缺血性脑损伤中干细胞靶向迁移的疗效。

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