Stem Cells from Human Exfoliated Deciduous Teeth Alleviate High-Altitude Cerebral Oedema by Shifting Microglial M1/M2 Polarisation.

Yi Ming Wang, Yi Kun Zhou, Chun Shan Han, Liu Jing Chen, Zi Meng Zhuang, Rui Li Yang, Wei Ran Li
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Abstract

Objective: To explore the high-efficiency and low-risk prevention and treatment strategies for stem cells from human exfoliated deciduous teeth (SHED) for high-altitude cerebral oedema.

Methods: A low-pressure and low-oxygen tank mimicking high-altitude conditions was used to establish the high-altitude cerebral oedema animal model. The preventive effects of SHED for cerebral oedema were then evaluated by haematoxylin and eosin (H&E) and histological staining. In vitro, SHED was co-cultured with BV-2 to analyse the effects of SHED by western blot and immunofluorescence staining.

Results: SHED can prevent and treat cerebral oedema in a high altitude rat animal model. Mechanistically, SHED treatment can protect brain cells from apoptosis induced by high altitude condition. Moreover, SHED treatment can inhibit M1-type polarisation and promote M2-type polarisation of microglia cells via the suppression of hypoxia inducible factor (HIF)- 1α-mediated extracellular signal-regulated kinase (ERK) signalling activated in high altitude condition.

Conclusion: SHED treatment can relieve high-altitude cerebral oedema via inhibiting HIF- 1α-mediated ERK signalling, which indicates that SHED is a promising alternative strategy to prevent and treat high-altitude cerebral oedema.

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来自人类脱落乳牙的干细胞通过转移小胶质细胞M1/M2极化来缓解高原脑水肿。
目的:探讨人脱落乳牙干细胞治疗高海拔脑水肿的高效、低风险的防治策略。方法:采用模拟高空条件的低压低氧罐建立高空脑水肿动物模型。然后通过苏木精和伊红(H&E)以及组织学染色来评估SHED对脑水肿的预防作用。在体外,SHED与BV-2共培养,通过蛋白质印迹和免疫荧光染色分析SHED的作用。结果:SHED可预防和治疗高原大鼠脑水肿动物模型。从机制上讲,SHED治疗可以保护脑细胞免受高原条件诱导的细胞凋亡。此外,SHED处理可以通过抑制在高海拔条件下激活的缺氧诱导因子(HIF)-1α介导的细胞外信号调节激酶(ERK)信号传导来抑制小胶质细胞的M1型极化,并促进M2型极化。结论:SHED治疗可以通过抑制HIF-1α介导的ERK信号传导来缓解高海拔脑水肿,这表明SHED是一种很有前途的预防和治疗高海拔脑出血的替代策略。
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