Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Appl Biochem Biotechnol. 2011 Mar;163(5):636-48. doi: 10.1007/s12010-010-9069-y. Epub 2010 Sep 5.
The effectiveness of Resovist-labeled bone marrow stem cells (BMSCs) was evaluated in vivo following their cerebral transplantation in a model of Parkinson's disease (PD) in rats using MRI, and the MRI findings were further compared with the behavior and histopathological manifestations of these rats. Forty PD rats were randomly assigned into five groups according to the cell doses injected into the rat brain site: control group (normal saline injection) and groups injected with 1 × 10(5), 1.5 × 10(5), 2 × 10(5), and 2.5 × 10(5) BMSCs. Gradient echo T2-weighted images were obtained immediately after cell transplantation and repeatedly taken 1, 4, 8, and 12 week(s) after cell transplantation. The rotational behavior of the animals was observed before and 1, 4, and 8 week(s) after transplantation. The rats were killed after the last MRI scanning, the brain tissues were analyzed by histopathology techniques, and RNAs were extracted for the expression analysis of selected genes using RT-PCR. One week following cell transplantation, all injected sites showed well-defined hypointense areas on MR images, with the most significant effect observed in rats injected with 2 × 10(5) BMSCs. These MR findings in PD rats lasted up to 12 weeks. The effectiveness of BMSC transplantation revealed by MRI was well confirmed by the behavioral and histopathological observations as well as indirectly supported by gene expression analyses. With the use of SPIO labeling, MRI techniques provided a dynamic evaluation of the spatial and temporal changes following cell transplantation and allowed the association analysis among the imaging, functions, and gene expression analysis in rats. These data also suggest the therapeutic potential of transplanted BMSCs. It is reasonable to speculate that the use of MRI in in vivo evaluation of the effect and fate of transplanted cells in various disease models will be beneficial to developing new strategies of cell-based gene therapy.
将 Resovist 标记的骨髓基质细胞(BMSCs)移植到帕金森病(PD)大鼠模型的大脑中后,通过 MRI 评估其体内有效性,并将 MRI 结果与这些大鼠的行为和组织病理学表现进一步进行比较。40 只 PD 大鼠随机分为 5 组,根据向大鼠脑内注射的细胞剂量:对照组(生理盐水注射)和注射 1×10(5)、1.5×10(5)、2×10(5)和 2.5×10(5)BMSCs 的组。细胞移植后立即获得梯度回波 T2 加权图像,并在细胞移植后 1、4、8 和 12 周重复采集。在移植前后观察动物的旋转行为。在最后一次 MRI 扫描后处死大鼠,通过组织病理学技术分析脑组织,并提取 RNA 用于 RT-PCR 分析选定基因的表达。细胞移植后 1 周,所有注射部位在 MRI 图像上均显示出明显的低信号区域,在注射 2×10(5)BMSCs 的大鼠中观察到最显著的效果。这些 PD 大鼠的 MRI 发现持续到 12 周。MRI 观察到的 BMSC 移植效果通过行为和组织病理学观察得到了很好的证实,也通过基因表达分析得到了间接支持。使用 SPIO 标记,MRI 技术可对细胞移植后的空间和时间变化进行动态评估,并允许对大鼠的成像、功能和基因表达分析进行关联分析。这些数据还表明了移植 BMSCs 的治疗潜力。合理推测,MRI 技术在各种疾病模型中用于体内评估移植细胞的效果和命运,将有利于开发基于细胞的基因治疗新策略。