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牙髓干细胞在阿尔茨海默病细胞模型上促进受损神经元细胞的再生。

Dental pulp stem cells promote regeneration of damaged neuron cells on the cellular model of Alzheimer's disease.

作者信息

Wang Feixiang, Jia Yali, Liu Jiajing, Zhai Jinglei, Cao Ning, Yue Wen, He Huixia, Pei Xuetao

机构信息

Department of Stomatology, Chinese PLA General Hospital and Chinese PLA Medical School, 28, Fuxing Road, Beijing, 100853, China.

Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Academy of Military Medical Sciences, 27, Taiping Road, Beijing, 100850, China.

出版信息

Cell Biol Int. 2017 Jun;41(6):639-650. doi: 10.1002/cbin.10767. Epub 2017 Apr 11.

Abstract

Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)-induced damage to human neuroblastoma cell line, SH-SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co-culture with hDPSCs by transwell co-culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs-treated cells were found to restore gradually with re-elongation of retracted dendrites. Meanwhile, Cell Counting Kit-8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs-treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α-tubulin and F-actin demonstrated that the hDPSCs-treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD.

摘要

阿尔茨海默病(AD)是一种无法治愈的神经退行性疾病,多种干细胞已被用于AD治疗并取得了一些良好效果。在本研究中,我们调查了人牙髓干细胞(hDPSCs)对体外经冈田酸(OA)诱导损伤人神经母细胞瘤细胞系SH-SY5Y 24小时建立的AD细胞模型的潜在治疗作用。确认AD细胞模型后,通过Transwell共培养系统将细胞与hDPSCs共培养24小时进行处理。然后发现经hDPSCs处理的细胞的细胞形态随着缩回树突的重新伸长而逐渐恢复。同时,细胞计数试剂盒-8检测和Hoechst 33258染色显示,hDPSCs分别使模型细胞的活力显著增加和凋亡减少。DiI标记观察也显示经hDPSCs处理的细胞中树突延长,这与AD模型细胞中的缩回树突明显不同。此外,α-微管蛋白和F-肌动蛋白的特异性染色表明,经hDPSCs处理的细胞具有恢复的神经元形态,树突伸长,微丝排列密集,微管纤维增粗。此外,蛋白质印迹结果显示,添加hDPSCs可显著抑制Tau蛋白Ser 396位点的磷酸化。这些结果表明,hDPSCs可能促进AD体外模型中受损神经元细胞的再生,并可能成为治疗AD的有用细胞来源。

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