Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke.

源自间充质干细胞（MSC）的外泌体和细胞外纳米囊泡（NV）可用于治疗缺血性中风，因为它们具有多方面的治疗益处，包括诱导血管生成，抗凋亡和抗炎作用。然而，使用外泌体和NV用于缺血性中风的最严重的缺点是全身给药后针对脑缺血性病变的靶向性差，从而产生不良的治疗结果。在这项研究中，我们表明，具有氧化铁纳米颗粒（IONP）的MSC衍生的磁性NV（MNV）可以大大改善缺血性病变的靶向性和治疗效果。因为IONP刺激了MSC中治疗性生长因子的表达，所以与来自原始MSC的NV相比，MNV包含更多的治疗性分子。在向短暂性中脑动脉闭塞（MCAO）诱导的大鼠中全身注射MNV之后，磁导航使MNV在缺血性病变处的定位增加了5.1倍。MNV注射和随后的磁导航促进了缺血性脑病灶中的抗炎反应，血管生成和抗凋亡，从而显着减少了梗塞体积并改善了运动功能。总的来说，所提出的MNV方法可以克服用于治疗缺血性中风的常规MSC-外来体疗法或NV疗法的主要缺点。MNV注射和随后的磁导航促进了缺血性脑病灶中的抗炎反应，血管生成和抗凋亡，从而显着减少了梗塞体积并改善了运动功能。总的来说，所提出的MNV方法可以克服用于治疗缺血性中风的常规MSC-外来体疗法或NV疗法的主要缺点。MNV注射和随后的磁导航促进了缺血性脑病灶中的抗炎反应，血管生成和抗凋亡，从而显着减少了梗塞体积并改善了运动功能。总的来说，所提出的MNV方法可以克服用于治疗缺血性中风的常规MSC-外来体疗法或NV疗法的主要缺点。