Hypoxia-preconditioned olfactory mucosa mesenchymal stem cells abolish cerebral ischemia/reperfusion-induced pyroptosis and apoptotic death of microglial cells by activating HIF-1α
Hypoxia-preconditioned olfactory mucosa mesenchymal stem cells abolish cerebral ischemia/reperfusion-induced pyroptosis and apoptotic death of microglial cells by activating HIF-1α
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DOI：
10.18632/aging.103307
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发表时间：
2020-06-15
期刊：
影响因子：
5.2
通讯作者：
Hu, Zhiping
中科院分区：
文献类型：
--
作者：
Huang, Yan;Tan, Fengbo;Hu, Zhiping
小胶质细胞是脑缺血/再灌注损伤后启动炎症反应的第一线免疫细胞。小胶质细胞还与称为焦亡的促炎性程序性细胞死亡的新亚型相关。研究一直致力于开发调节炎症反应和防止脑I/R引起的细胞死亡的治疗方法。这些治疗中的关键包括间充质干细胞（MSC）治疗。嗅粘膜间充质干细胞（OM-MSC）是一种独特类型的MSC，通过促进旁分泌因子的分泌和神经保护作用来赋予神经保护作用。本研究探讨了缺氧OM-MSCs是否可以抑制小胶质细胞在体外I/R损伤后的死亡。建立一种类似于缺血再灌注（I/R）的传统氧糖剥夺/再灌注（OGD/R）模型。结果表明，OGD/R诱导小胶质细胞凋亡和焦亡，而OM-MSC缺氧显着减弱了这些作用。此外，OM-MSCs的作用由缺氧诱导因子1-α（HIF-1 α）介导。总之，这些发现表明，缺氧预处理的OM-MSC抑制小胶质细胞的pyroptotic和凋亡性死亡，在脑缺血/再灌注损伤通过激活HIF-1 α在体外。
Microglial cells are the first line immune cells that initiate inflammatory responses following cerebral ischemia/reperfusion(I/R) injury. Microglial cells are also associated with a novel subtype of pro-inflammatory programmed cell death known as pyroptosis. Research has been directed at developing treatments that modulate inflammatory responses and protect against cell death caused by cerebral I/R. Key among such treatments include mesenchymal stem cell (MSC) therapy. A unique type of MSC termed olfactory mucosa mesenchymal stem cell (OM-MSC) confers neuroprotection by promoting the secretion of paracrine factors, and neuroprotection. This study investigated whether hypoxic OM-MSCs could inhibit microglial cell death upon I/R insult in vitro. A traditional oxygen-glucose deprivation/reperfusion (OGD/R) model, analogous to I/R, was established. Results showed that OGD/R induced apoptosis and pyroptosis in microglial cells while hypoxia in OM-MSCs significantly attenuated these effects. Moreover, the effects of OM-MSCs were mediated by Hypoxia-inducible factor 1-alpha (HIF-1 alpha). Taken together, these findings reveal that hypoxia-preconditioned OM-MSC inhibits pyroptotic and apoptotic death of microglial cell in response to cerebral ischemia/reperfusion insult by activating HIF-1 alpha in vitro.