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MRI Tracking of SPIO- and Fth1-Labeled Bone Marrow Mesenchymal Stromal Cell Transplantation for Treatment of Stroke.
Contrast Media & Molecular Imaging ( IF 3.009 ) Pub Date : 2019-08-29 , DOI: 10.1155/2019/5184105
Xiaolei Huang 1 , Yang Xue 2 , Jinliang Wu 2 , Qing Zhan 2, 3 , Jiangmin Zhao 4, 5
Affiliation  

We aimed to identify a suitable method for long-term monitoring of the migration and proliferation of mesenchymal stromal cells in stroke models of rats using ferritin transgene expression by magnetic resonance imaging (MRI). Bone marrow mesenchymal stromal cells (BMSCs) were transduced with a lentivirus containing a shuttle plasmid (pCDH-CMV-MCS-EF1-copGFP) carrying the ferritin heavy chain 1 (Fth1) gene. Ferritin expression in stromal cells was evaluated with western blotting and immunofluorescent staining. The iron uptake of Fth1-BMSCs was measured with Prussian blue staining. Following surgical introduction of middle cerebral artery occlusion, Fth1-BMSCs and superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected through the internal jugular vein. The imaging and signal intensities were monitored by diffusion-weighted imaging (DWI), T2-weighted imaging (T2WI), and susceptibility-weighted imaging (SWI) in vitro and in vivo. Pathology was performed for comparison. We observed that the MRI signal intensity of SPIO-BMSCs gradually reduced over time. Fth1-BMSCs showed the same signal intensity between 10 and 60 days. SWI showed hypointense lesions in the SPIO-BMSC (traceable for 30 d) and Fth1-BMSC groups. T2WI was not sensitive enough to trace Fth1-BMSCs. After transplantation, Prussian blue-stained cells were observed around the infarction area and in the infarction center in both transplantation models. Fth1-BMSCs transplanted for treating focal cerebral infarction were safe, reliable, and traceable by MRI. Fth1 labeling was more stable and suitable than SPIO labeling for long-term tracking. SWI was more sensitive than T2W1 and suitable as the optimal MRI-tracking sequence.

中文翻译:

SPIO和Fth1标签的骨髓间质基质细胞移植的MRI追踪治疗中风。

我们旨在确定一种合适的方法,用于通过磁共振成像(MRI)使用铁蛋白转基因表达来长期监测大鼠中风模型中的间充质基质细胞的迁移和增殖。用含有携带铁蛋白重链1(Fth1)基因的穿梭质粒(pCDH-CMV-MCS-EF1-copGFP)的慢病毒转导骨髓间充质基质细胞(BMSC)。通过蛋白质印迹和免疫荧光染色评估基质细胞中铁蛋白的表达。用普鲁士蓝染色测量Fth1-BMSCs的铁摄取。通过外科手术引入大脑中动脉闭塞后,通过颈内静脉注射Fth1-BMSC和超顺磁性氧化铁(SPIO-)标记的BMSC。通过扩散加权成像(DWI)监控成像和信号强度,T2加权成像(T2WI),以及体外和体内磁化率加权成像(SWI)。进行病理学进行比较。我们观察到,SPIO-BMSC的MRI信号强度会随着时间逐渐降低。Fth1-BMSC在10到60天之间显示出相同的信号强度。SWI在SPIO-BMSC组(可追踪30 d)和Fth1-BMSC组中显示出低水平病变。T2WI不够灵敏,无法追踪Fth1-BMSC。移植后,在两种移植模型中,在梗塞区域周围和梗塞中心均观察到普鲁士蓝染色的细胞。移植用于治疗局灶性脑梗死的Fth1-BMSC安全,可靠且可通过MRI追溯。Fth1标记比SPIO标记更稳定,更适合长期跟踪。SWI比T2W1敏感,适合作为最佳MRI跟踪序列。
更新日期:2019-11-01
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