In Vivo Long-Term Tracking of Neural Stem Cells Transplanted into an Acute Ischemic Stroke model with Reporter Gene-Based Bimodal MR and Optical Imaging.

In Vivo Long-Term Tracking of Neural Stem Cells Transplanted into an Acute Ischemic Stroke model with Reporter Gene-Based Bimodal MR and Optical Imaging.
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利用基于报告基因的双模态磁共振和光学成像对移植到急性缺血性中风的神经干细胞进行体内长期跟踪

DOI:
10.1177/0963689717722560
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发表时间:
2017-10
影响因子:
3.3
通讯作者:
Shen J
Shen J
中科院分区:
医学4区
文献类型:
--
作者:
Zhang F;Duan X;Lu L;Zhang X;Chen M;Mao J;Cao M;Shen J

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神经干细胞移植(NSCs)是治疗中风的一种新方法。移植神经干细胞的实时成像对于成功的细胞传递、安全监测、跟踪细胞命运和功能以及了解移植细胞与宿主环境的相互作用是必不可少的。磁性纳米颗粒标记细胞的磁共振成像(MRI)已成为体内追踪干细胞的最广泛使用的手段。然而,它不允许对活细胞和死亡细胞进行可靠的区分。基于报告基因的MRI被认为是克服这一缺点的一种替代策略。本工作构建了一类编码铁蛋白重链(FTH)和增强型绿色荧光蛋白(EGFP)的慢病毒载体,将报告基因导入神经干细胞。将这些转基因神经干细胞移植到急性缺血性卒中大鼠的对侧大脑半球,在体内进行MRI和荧光成像(FLI),追踪移植细胞在6wk长时间内的命运。结果表明,通过所设计的慢病毒载体,FTH和EGFP可以有效和安全地输送到神经干细胞。移植干细胞的分布和迁移可通过双峰MRI和荧光成像进行监测。FTH可以作为一种强大的MRI报告程序,可靠地报告细胞移植的短期活性,而其跟踪干细胞长期活性的能力仍然依赖于几个混杂因素,如细胞死亡和伴随的反应性炎症。
Transplantation of neural stem cells (NSCs) is emerging as a new therapeutic approach for stroke. Real-time imaging of transplanted NSCs is essential for successful cell delivery, safety monitoring, tracking cell fate and function, and understanding the interactions of transplanted cells with the host environment. Magnetic resonance imaging (MRI) of magnetic nanoparticle-labeled cells has been the most widely used means to track stem cells in vivo. Nevertheless, it does not allow for the reliable discrimination between live and dead cells. Reporter gene-based MRI was considered as an alternative strategy to overcome this shortcoming. In this work, a class of lentiviral vector-encoding ferritin heavy chain (FTH) and enhanced green fluorescent protein (EGFP) was constructed to deliver reporter genes into NSCs. After these transgenic NSCs were transplanted into the contralateral hemisphere of rats with acute ischemic stroke, MRI and fluorescence imaging (FLI) were performed in vivo for tracking the fate of transplanted cells over a long period of 6 wk. The results demonstrated that the FTH and EGFP can be effectively and safely delivered to NSCs via the designed lentiviral vector. The distribution and migration of grafted stem cells could be monitored by bimodal MRI and FLI. FTH can be used as a robust MRI reporter for reliable reporting of the short-term viability of cell grafts, whereas its capacity for tracking the long-term viability of stem cells remains dependent on several confounding factors such as cell death and the concomitant reactive inflammation.
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