Mesenchymal Stem Cell-derived Exosomes Rescue Oxygen-Glucose Deprivation-induced Injury in Endothelial Cells
Mesenchymal Stem Cell-derived Exosomes Rescue Oxygen-Glucose Deprivation-induced Injury in Endothelial Cells
复制标题
间充质干细胞衍生的外泌体可挽救缺氧葡萄糖诱导的内皮细胞损伤
DOI：
10.2174/1567202617666200214103950
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发表时间：
2020-01-01
影响因子：
2.1
通讯作者：
Liu, Zi-you
中科院分区：
文献类型：
--
作者：
Kong, Li-yun;Liang, Meng-ya;Liu, Zi-you
目的：体外模拟深低温停循环（DHCA）细胞，间充质干细胞（MSC）来源的外泌体对氧糖剥夺（OGD）下脑微血管内皮细胞的影响尚待研究。方法：将MSC与原代大鼠脑内皮细胞共培养，然后将其暴露于OGD。测定细胞活力、细胞凋亡、炎症因子（IL-1β、IL-6 和 TNF-α）以及炎症相关 TLR4 介导的细胞焦亡和 NF-κ B 信号通路的激活。此外，分离源自 MSC 的外泌体并与内皮细胞一起孵育，以研究 MSC 的作用是否与 MSC 衍生的外泌体相关。还分析了 OGD 诱导的内皮细胞与 MSC 衍生的外泌体一起孵育的细胞凋亡、细胞活力和炎症反应。结果：OGD 处理促进内皮细胞凋亡，诱导炎症因子 IL-1β、IL-6 和 TNF-α 的释放，并抑制细胞活力。 Western blot分析显示OGD处理诱导TLR4和NF-KB p65亚基磷酸化和caspase-1上调，而与MSC共培养可以降低OGD处理对内皮细胞的影响。正如预期的那样，MSC 衍生的外泌体对 OGD 处理的内皮细胞的影响与 MSC 相似。 MSC衍生的外泌体减轻了OGD诱导的内皮细胞活力下降，并增加了细胞凋亡、炎症因子水平以及炎症和炎症局灶通路的激活。结论：MSC和MSC衍生的外泌体均减轻了OGD诱导的大鼠原发性脑内皮细胞损伤。这些发现表明，间充质干细胞衍生的外泌体至少介导间充质干细胞对内皮细胞的部分保护作用。
Objective: The effects of mesenchymal stem cell (MSC)-derived exosomes on brain microvascular endothelial cells under oxygen-glucose deprivation (OGD), which mimic cells in deep hypothermic circulatory arrest (DHCA) in vitro, are yet to be studied.Methods: MSCs were co-cultured with primary rat brain endothelial cells, which were then exposed to OGD. Cell viability, apoptosis, the inflammatory factors (IL-1 beta, IL-6, and TNF-alpha), and the activation of inflammation-associated TLR4-mediated pyroptosis and the NF-kappa B signaling pathway were determined. Furthermore, exosomes derived from MSCs were isolated and incubated with endothelial cells to investigate whether the effect of MSCs is associated with MSC-derived exosomes. Apoptosis, cell viability, and the inflammatory response were also analyzed in OGD-induced endothelial cells incubated with MSC-derived exosomes.Results: OGD treatment promoted endothelial cell apoptosis, induced the release of inflammatory factors IL-1 beta, IL-6, and TNF-alpha, and inhibited cell viability. Western blot analysis showed that OGD treatment-induced TLR4, and NF-KB p65 subunit phosphorylation and caspase-1 upregulation, while co-culture with MSCs could reduce the effect of OGD treatment on endothelial cells. As expected, the effect of MSC-derived exosomes on OGD-treated endothelial cells was similar to that of MSCs. MSC-derived exosomes alleviated the OGD-induced decrease in the viability of endothelial cells, and increased levels of apoptosis, inflammatory factors, and the activation of inflammatory and inflammatory focal pathways.Conclusion: Both MSCs and MSC-derived exosomes attenuated OGD-induced rat primary brain endothelial cell injury. These findings suggest that MSC-derived exosomes mediate at least some of the protective effects of MSCs on endothelial cells.