Wang Jiayi, Zhao Mengke, Fu Dong, Wang Meina, Han Chao, Lv Zhongyue, Wang Liang, Liu Jing
Stem Cell Clinical Research Center, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
Dalian Innovation Institute of Stem Cell and Precision Medicine, Dalian, Liaoning Province, China.
Neural Regen Res. 2025 Nov 1;20(11):3245-3258. doi: 10.4103/NRR.NRR-D-23-01144. Epub 2024 Sep 6.
JOURNAL/nrgr/04.03/01300535-202511000-00028/figure1/v/2024-12-20T164640Z/r/image-tiff Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells, and can thus be used as substitutes for stem cells in stem cell therapy, thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments. This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke. However, the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear, presenting challenges for clinical translation. To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside, we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke. We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis. The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase, mammalian target of rapamycin, and protein kinase B, and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor. These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Finally, we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile. Therefore, human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.
《神经再生研究》/nrgr/04.03/01300535 - 202511000 - 00028/图1/v/2024 - 12 - 20T164640Z/图像 - 标签 人神经干细胞衍生的细胞外囊泡具有与其亲代细胞类似的功能，因此可在干细胞治疗中用作干细胞的替代品，从而降低干细胞治疗的风险并推进干细胞衍生治疗的前沿。这为开发潜在有效的缺血性中风新治疗方式奠定了基础。然而，人神经干细胞衍生的细胞外囊泡疗效和安全性的精确机制仍不清楚，这给临床转化带来了挑战。为促进基于人神经干细胞衍生的细胞外囊泡的治疗从实验室到临床的转化，我们进行了一项全面的临床前研究，以评估人神经干细胞衍生的细胞外囊泡治疗缺血性中风的疗效和安全性。我们发现，将人神经干细胞衍生的细胞外囊泡给予缺血性中风大鼠模型可减少脑梗死体积，并通过减轻神经元凋亡促进功能恢复。人神经干细胞衍生的细胞外囊泡通过增强磷脂酰肌醇3 -激酶、雷帕霉素靶蛋白和蛋白激酶B的磷酸化来减少神经元凋亡，而用磷脂酰肌醇3 -激酶抑制剂处理可逆转这些作用。这些发现表明，人神经干细胞衍生的细胞外囊泡通过激活磷脂酰肌醇3 -激酶/蛋白激酶B/雷帕霉素靶蛋白信号通路在缺血性中风中发挥神经保护作用。最后，我们表明人神经干细胞衍生的细胞外囊泡在体内具有良好的安全性。因此，人神经干细胞衍生的细胞外囊泡是治疗缺血性中风的一种有前景的潜在药物。
