首页> 外文期刊>Neuropathology: official journal of the Japanese Society of Neuropathology >Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct
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Timing and cell dose determine therapeutic effects of bone marrow stromal cell transplantation in rat model of cerebral infarct

机译:时间和细胞剂量决定了骨髓基质细胞移植对脑梗死大鼠模型的治疗作用

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Stereotactic transplantation of bone marrow stromal cells (BMSCs) enables efficient delivery to the infarct brain. This study was aimed to assess its optimal timing and cell dose for ischemic stroke. The BMSCs were harvested from the green fluorescent protein-transgenic rats and were labeled with quantum dots. The BMSCs (1×105 or 1×106) were stereotactically transplanted into the ipsilateral striatum of the rats subjected to permanent middle cerebral artery occlusion at 1 or 4 weeks post-ischemia. Motor function was serially assessed. Using in vivo near infrared (NIR) fluorescence imaging, the engrafted BMSCs were visualized at 3 weeks post-transplantation. Immunohistochemistry was performed to evaluate their fate. Functional recovery was significantly enhanced when both low and high doses of BMSCs were transplanted at 1 week post-ischemia, but such therapeutic effects were observed only when the high-dose BMSCs were transplanted at 4 weeks post-ischemia. Both optical imaging and immunohistochemistry revealed their better engraftment in the peri-infarct area when the high-dose BMSCs were transplanted at 1 or 4 weeks post-ischemia. These findings strongly suggest the importance of timing and cell dose to yield therapeutic effects of BMSC transplantation for ischemic stroke. Earlier transplantation requires a smaller number of donor cells for beneficial effects.
机译:骨髓基质细胞(BMSCs)的立体定向移植能够有效地输送到梗塞的大脑。本研究旨在评估其对缺血性中风的最佳时机和细胞剂量。从绿色荧光蛋白转基因大鼠中收获BMSC,并用量子点标记。在缺血后1或4周,将BMSC(1×105或1×106)立体定向移植到大鼠永久性大脑中动脉闭塞的同侧纹状体中。连续评估运动功能。使用体内近红外(NIR)荧光成像,在移植后3周时观察移植的BMSC。进行免疫组织化学以评估其命运。当在缺血后1周移植低剂量和高剂量的BMSC时,功能恢复显着增强,但是只有在缺血后4周移植高剂量的BMSC时,才观察到这种治疗效果。当在缺血后1或4周移植大剂量BMSC时,光学成像和免疫组织化学均显示它们在梗死周围区域的植入效果更好。这些发现强烈表明时机和细胞剂量对于产生BMSC移植治疗缺血性中风的重要性。较早的移植需要较少数量的供体细胞以获得有益效果。

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