中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (6): 909-915.doi: 10.4103/1673-5374.158355

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

磁共振示踪Ferumoxytol标记人脂肪来源干细胞移植脑梗死大鼠脑内是可行的

  

  • 收稿日期:2015-03-11 出版日期:2015-06-18 发布日期:2015-06-18
  • 基金资助:

    大连市科技计划项目(2014E14SF186)

In vivo tracking of human adipose-derived stem cells labeled with ferumoxytol in rats with middle cerebral artery occlusion by magnetic resonance imaging

Yan Yin 1, Xiang Zhou 2, Xin Guan 3, Yang Liu 4, Chang-bin Jiang 2, Jing Liu 4   

  1. 1 Department of Neurology, the Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
    2 Department of Neurology, the First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
    3 College of Life Sciences, Liaoning Normal University, Dalian, Liaoning Province, China
    4 Regenerative Medicine Center, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China
  • Received:2015-03-11 Online:2015-06-18 Published:2015-06-18
  • Contact: Chang-bin Jiang or Jing Liu, M.D., jchangbinvip@163.com or liujingdalian@163.com.
  • Supported by:

     This study was supported by the Science and Technology Plan Project of Dalian City in China, No. 2014E14SF186.

摘要:

最近,FDA批准了铁替代疗法专用药物之一新型超顺磁性氧化铁即Ferumoxytol,此药属铁替代疗法专用药物之一。我们旨在证明ferumoxytol标记人脂肪来源干细胞移植入大脑中动脉闭塞大鼠脑内,利用3.0T磁共振示踪标记这种干细胞的可行性。实验将104个Ferumoxytol-肝素-鱼精蛋白纳米复合物标记的人脂肪来源干细胞立体定位移植入大脑中动脉闭塞大鼠脑内,移植成功后分别在1,7,14,28 d分别进行进行神经功能缺损评分,T2WI和增强梯度回波T2*加权血管成像序列动态观察移植细胞,并将所得到的影像学检查结果与脑组织切片普鲁士蓝染色结果进行对照。结果发现,除移植1 d外,其他时间点移植干细胞大鼠的改良神经功能缺损程度评分均较未移植干细胞大鼠显著降低。移植后的MRI低信号区经普鲁士蓝染色证实为Ferumoxytol-肝素-鱼精蛋白标记的人脂肪来源干细胞,增强梯度回波T2*加权血管成像较T2WI能更好地示踪Ferumoxytol-肝素-鱼精蛋白标记干细胞。结果证实,Ferumoxytol标记人脂肪来源干细胞并移植入大脑中动脉闭塞大鼠脑内,利用3.0 T磁共振示踪这种标记干细胞的方法是可行的。

关键词: 神经再生, 脑损伤, 神经影像学, Ferumoxytol, 超顺磁性氧化铁颗粒, 人脂肪源性干细胞, 大脑中动脉闭塞, 脑内注射, 磁共振, 磁敏感加权成像图像增强, 改良神经功能缺损程度评分, 大鼠, 普鲁士蓝染色

Abstract:

Ferumoxytol, an iron replacement product, is a new type of superparamagnetic iron oxide approved by the US Food and Drug Administration. Herein, we assessed the feasibility of tracking transplanted human adipose-derived stem cells labeled with ferumoxytol in middle cerebral artery occlusion-injured rats by 3.0 T MRI in vivo. 1 × 104 human adipose-derived stem cells labeled with ferumoxytol-heparin-protamine were transplanted into the brains of rats with middle cerebral artery occlusion. Neurologic impairment was scored at 1, 7, 14, and 28 days after transplantation. T2-weighted imaging and enhanced susceptibility-weighted angiography were used to observe transplanted cells. Results of imaging tests were compared with results of Prussian blue staining. The modified neurologic impairment scores were significantly lower in rats transplanted with cells at all time points except 1 day post-transplantation compared with rats without transplantation. Regions with hypointense signals on T2-weighted and enhanced susceptibility-weighted angiography images corresponded with areas stained by Prussian blue, suggesting the presence of superparamagnetic iron oxide particles within the engrafted cells. Enhanced susceptibility-weighted angiography image exhibited better sensitivity and contrast in tracing ferumoxytol-heparin-protamine-labeled human adipose-derived stem cells compared with T2-weighted imaging in routine MRI.

Key words: nerve regeneration, brain injury, neuroimaging, ferumoxytol, superparamagnetic iron oxide particles, human adipose-derived stem cells, middle cerebral artery occlusion, intracerebral  , injection, magnetic resonance imaging, enhanced susceptibility-weighted angiography image, modified neurological severity scores, rats, Prussian blue staining, neural regeneration