Department of Neurology, Seoul National University Hospital, Seoul 03080, Korea.
Department of Neurology, Seoul National University College of Medicine, Seoul 03080, Korea.
Int J Mol Sci. 2020 May 22;21(10):3658. doi: 10.3390/ijms21103658.
This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.
本研究评估了负载氧化铁纳米颗粒的人胚胎干细胞（ESC）衍生的球形神经球（SNM）在改善干细胞向大脑输送、减轻脑出血（ICH）引起的脑损伤以及在附着于头盔的磁铁的外部磁场下恢复 ICH 后功能状态方面的潜力。ICH 诱导后 24 小时，大鼠被随机分为三组实验：注射磷酸盐缓冲液（PBS 组）、静脉注射磁铁矿样亚铁磁性氧化铁纳米立方体（FION）标记的 SNM（SNM组）和静脉注射 FION 标记的 SNM 后，通过嵌入磁铁的头盔进行三天的外部磁场靶向输送（SNM+Helmet 组）。ICH 诱导后第 3 天，SNM*+Helmet 组的普鲁士蓝染色面积增加和肿胀体积减小。与其他组相比，SNM*+Helmet 组在 ICH 后三天观察到巨噬细胞和中性粒细胞募集减少，促炎细胞因子下调，神经功能改善。ICH 后六周，SNM*+Helmet 组半球萎缩明显低于 PBS 组。总之，我们开发了一种使用标记有铁蛋白的干细胞和嵌入磁铁的头盔的靶向输送系统。SNM 的靶向输送可能为开发 ICH 的新治疗策略提供了潜力。
