Emerging stroke literature suggests that treatment of experimentally induced stroke with stem cells offered post-stroke neuroprotection via exosomes produced by these cells. Treatment with exosomes has great potential to overcome the limitations associated with cell-based therapies. However, in our preliminary studies, we noticed that the exosomes released from human umbilical cord blood-derived mesenchymal stem cells (MSCs) under standard culture conditions did not improve the post-stroke neurological outcome. Because of this apparent discrepancy, we hypothesized that exosome characteristics vary with the conditions of their production. Specifically, we suggest that the exosomes produced from the cocultures of regular and oxygen–glucose-deprived (OGD) MSCs in vitro would represent the exosomes produced from MSCs that are exposed to ischemic brain cells in vivo, and offer similar therapeutic benefits that the cell treatment would provide. We tested the efficacy of therapy with exosomes secreted from human umbilical cord blood (HUCB)-derived MSCs under in vitro hypoxic conditions on post-stroke brain damage and neurological outcome in a rat model of transient focal cerebral ischemia. We performed the TTC staining procedure as well as the neurological tests including the modified neurological severity scores (mNSS), the modified adhesive removal (sticky-tape), and the beam walking tests before ischemia and at regular intervals until 7 days reperfusion. Treatment with exosomes obtained from the cocultures of normal and OGD-induced MSCs reduced the infarct size and ipsilateral hemisphere swelling, preserved the neurological function, and facilitated the recovery of stroke-induced rats. Based on the results, we conclude that the treatment with exosomes secreted from MSCs at appropriate experimental conditions attenuates the post-stroke brain damage and improves the neurological outcome.

中文翻译：

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正常和缺氧缺氧干细胞共培养分泌的外泌体可改善中风后的结局。

新兴的中风文献表明，用干细胞治疗实验性中风可通过这些细胞产生的外来体提供中风后神经保护作用。外泌体治疗具有巨大的潜力，可以克服与基于细胞的疗法相关的局限性。但是，在我们的初步研究中，我们注意到在标准培养条件下从人脐血来源的间充质干细胞（MSC）释放的外泌体并不能改善卒中后神经系统的预后。由于这种明显的差异，我们假设外泌体特征随其生产条件而变化。特别，我们建议常规和缺氧缺氧（OGD）MSC体外共培养产生的外泌体将代表由MSC体内暴露于体内缺血性脑细胞的外泌体，并提供与细胞治疗相似的治疗益处提供。我们在短暂性局灶性脑缺血的大鼠模型中测试了在体外低氧条件下，人脐带血（HUCB）来源的MSC分泌的外泌体对中风后脑损伤和神经系统结局的治疗效果。我们进行了TTC染色程序以及神经系统测试，包括修改后的神经系统严重程度评分（mNSS），修改后的粘着剂去除（粘性胶带）以及局部缺血前和定期间隔直至7天再灌注的束步测试。用从正常和OGD诱导的MSC的共培养物中获得的外泌体进行治疗，可减少梗塞面积和同侧半球肿胀，保留神经功能，并促进中风诱导大鼠的恢复。根据结果​​，我们得出结论，在适当的实验条件下用MSC分泌的外泌体进行治疗，可减轻中风后脑损伤并改善神经功能。