Purpose: Mesenchymal stem cell-derived exosomes (MSC-exos) are considered an important restorative treatment for ischemic stroke. However, the migration ability and survival of exogenous MSC-exos remain unclear. Here, we investigated whether MSC-exos migrate into the ischemic brain and play a protective role against ischemic stroke.
Methods: MSC-exos labeled with DiR were injected intravenously into mice with ischemic stroke. Near-infrared fluorescence (NIRF) images were obtained on days 0, 1, 3, 5, 7, 10, and 14, and magnetic resonance (MR) images were obtained on days 1, 7 and 14. On day 14, the functional outcomes, angiogenesis, neurogenesis, and white matter remodeling were assessed, and Western blot assays were performed.
Results: Fluorescence signals from the MSC-exos appeared in the injured brain from day 1 and peaked on day 3. The immunofluorescence staining of the brain samples revealed that the MSC-exos were localized in neurons. The behavioral scores and T2-weighted imaging indicated that the MSC-exos improved neurological functional recovery after stroke. In addition, the in vivo MR-diffusion tensor imaging (DTI) indicated that the exogenous MSC-exos increased the fractional anisotropy (FA) value, fiber length, and fiber number ratio. Furthermore, in the mice with ischemic stroke treated with MSC-exos, angiogenesis and neurogenesis were significantly improved, and the expression of IL-1β was reduced.
Conclusion: MSC-exos can migrate into the brains of mice with ischemic stroke and exert therapeutic effects against ischemic stroke; therefore, MSC-exos may have broad clinical applications in the future.

Keywords: MSCs, exosomes, homing, near-infrared fluorescence, stroke, diffusion tensor imaging


中文翻译：

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分子成像对缺血性中风小鼠外源性间充质干细胞衍生外泌体的体内监测和评估

目的：间充质干细胞衍生的外泌体（MSC-exos）被认为是缺血性中风的重要恢复性治疗方法。然而，外源性MSC-exos的迁移能力和存活率仍不清楚。在这里，我们研究了 MSC-exos 是否迁移到缺血性脑中并对缺血性中风发挥保护作用。
方法：将DiR标记的MSC-exos静脉注射到缺血性卒中小鼠体内。在第 0、1、3、5、7、10 和 14 天获得近红外荧光 (NIRF) 图像，在第 1、7 和 14 天获得磁共振 (MR) 图像。在第 14 天，功能结果、血管生成、神经发生和白质重塑进行了评估，并进行了蛋白质印迹分析。
结果：来自 MSC-exos 的荧光信号从第 1 天开始出现在受伤的大脑中，并在第 3 天达到峰值。脑样本的免疫荧光染色显示 MSC-exos 定位于神经元中。行为评分和 T2 加权成像表明 MSC-exos 改善了中风后的神经功能恢复。此外，体内 MR 扩散张量成像 (DTI) 表明，外源性 MSC-exos 增加了分数各向异性 (FA) 值、纤维长度和纤维数比。此外，在用 MSC-exos 治疗的缺血性卒中小鼠中，血管生成和神经发生显着改善，IL-1β 的表达降低。
结论：MSC-exos可以迁移到缺血性中风小鼠的大脑中，对缺血性中风发挥治疗作用；因此，MSC-exos 未来可能具有广泛的临床应用。

关键词：间充质干细胞，外泌体，归巢，近红外荧光，中风，扩散张量成像