Background. Spinal cord injury (SCI) remains a challenge owing to limited therapies. The exosome of neural stem cells (NSCs-Exos) and FTY720 transplantation could improve SCI effectively. However, the effect and mechanism of NSCs-Exos combined with FTY720 (FTY720-NSCs-Exos) transplantation in the treatment of SCI are not fully understood. Methods. Sprague Dawley rats (8-week-old) were used to establish the SCI model, followed by the treatment of NSCs-Exos, FTY720, and FTY720-NSCs-Exos. The effect of FTY720, NSCs-Exos, and FTY720-NSCs-Exos combination treatment on hindlimb function, pathological changes, apoptosis activity, and the expression of spinal edema-related proteins and apoptosis-related proteins in SCI models were investigated by BBB scoring, HE staining, TUNEL staining and immunohistochemistry, and Western blotting. Meanwhile, the effect of these treatments on spinal cord microvascular endothelial cells (SCMECs) was detected under hypoxic circumstance. Results. Our results found that FTY720-NSCs-Exos could alleviate pathological alterations and ameliorate the hindlimb function and oxygen insufficiency in model mice after SCI. In addition, exosomes could ameliorate the morphology of neurons, reduce inflammatory infiltration and edema, decrease the expression of Bax and AQP-4, upregulate the expression of claudin-5 and Bcl-2, and inhibit cell apoptosis. At the same time, in vitro experiments showed that FTY720-NSCs-Exos could protect the barrier of SCMECs under hypoxic circumstance, and the mechanism is related to PTEN/AKT pathway. Conclusion. FTY720-NSCs-Exos therapy displayed a positive therapeutic effect on SCI by regulating PTEN/AKT pathway and offered a new therapy for SCI.

中文翻译：

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载有FTY720的神经干细胞衍生的外泌体通过PTEN/AKT信号通路促进大鼠脊髓损伤后的恢复

背景。由于治疗方法有限，脊髓损伤 (SCI) 仍然是一个挑战。神经干细胞外泌体（NSCs-Exos）和FTY720移植可有效改善SCI。然而，NSCs-Exos联合FTY720（FTY720-NSCs-Exos）移植治疗SCI的效果和机制尚不完全清楚。方法. 采用 Sprague Dawley 大鼠（8 周龄）建立 SCI 模型，然后分别处理 NSCs-Exos、FTY720 和 FTY720-NSCs-Exos。通过 BBB 评分研究 FTY720、NSCs-Exos 和 FTY720-NSCs-Exos 联合治疗对 SCI 模型中后肢功能、病理变化、凋亡活性以及脊髓水肿相关蛋白和凋亡相关蛋白表达的影响， HE染色、TUNEL染色和免疫组化，以及Western印迹。同时，在缺氧条件下检测这些治疗对脊髓微血管内皮细胞（SCMECs）的影响。结果. 我们的研究结果发现，FTY720-NSCs-Exos 可以减轻 SCI 后模型小鼠的病理改变并改善后肢功能和氧不足。此外，外泌体可以改善神经元形态，减少炎症浸润和水肿，降低Bax和AQP-4的表达，上调claudin-5和Bcl-2的表达，抑制细胞凋亡。同时体外实验表明FTY720-NSCs-Exos在缺氧环境下可以保护SCMECs的屏障，其机制与PTEN/AKT通路有关。结论。FTY720-NSCs-Exos疗法通过调节PTEN/AKT通路对SCI表现出积极的治疗作用，为SCI提供了一种新的治疗方法。