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中华细胞与干细胞杂志(电子版) ›› 2024, Vol. 14 ›› Issue (02) : 93 -106. doi: 10.3877/cma.j.issn.2095-1221.2024.02.005

综述

间充质干细胞缓解阿尔茨海默病氧化应激的新思路
王娟1, 刘晔1, 熊威1, 蒋财磊2, 贺燕2, 叶青松1,()   
  1. 1. 430060 武汉,湖北武汉大学人民医院再生医学中心;430060 武汉,湖北武汉大学人民医院口腔科
    2. 430064 武汉,湖北武汉科技大学附属天佑医院口腔科
  • 收稿日期:2024-02-09 出版日期:2024-04-01
  • 通信作者: 叶青松

A novel therapeutic mechanism for mesenchymal stem cells to alleviate oxidative stress in Alzheimer's disease

Juan Wang1, Ye Liu1, Wei Xiong1, Cailei Jiang2, Yan He2, Qingsong Ye1,()   

  1. 1. Center of Regenerative Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China; Department of Stomatology, Renmin Hospital of Wuhan University, Wuhan 430060, China
    2. Department of Stomatology, Tianyou Hospital of Wuhan University of Science and Technology, Wuhan 430064, China
  • Received:2024-02-09 Published:2024-04-01
  • Corresponding author: Qingsong Ye
引用本文:

王娟, 刘晔, 熊威, 蒋财磊, 贺燕, 叶青松. 间充质干细胞缓解阿尔茨海默病氧化应激的新思路[J]. 中华细胞与干细胞杂志(电子版), 2024, 14(02): 93-106.

Juan Wang, Ye Liu, Wei Xiong, Cailei Jiang, Yan He, Qingsong Ye. A novel therapeutic mechanism for mesenchymal stem cells to alleviate oxidative stress in Alzheimer's disease[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 93-106.

阿尔茨海默病(AD)是导致与年龄相关痴呆症的主要原因,其特征是进行性脑萎缩和认知功能障碍,最终导致患者无法自理。尽管一些药物治疗可缓解AD症状,但它们不能阻止AD的进展,且有多种副作用。基于AD存在多种致病机制假说,表明AD的进展不止受单一条件影响,而近期脑内氧化应激微环境备受瞩目,间充质干细胞(MSCs)由于其免疫调节、抗炎、再生、抗氧化、抗凋亡和神经保护等多重调节作用,可以改善脑内微环境,进而减少AD病理改变和改善认知功能障碍,可能成为治疗AD的潜在方案。MSCs尤其是牙髓干细胞(DPSCs)不仅分泌神经保护和抗炎因子以促进神经元存活,而且能促进小胶质细胞在蛋白质聚集物周围的积累并清除病理聚集物,还能缓解线粒体损伤。本综述重点关注使用MSCs以及潜在MSCs资源DPSCs通过改善氧化应激微环境来减缓AD的发展,为临床治疗AD提供新思路。

Alzheimer's disease (AD) is the leading cause of age-related dementia, which is characterized by progressive brain atrophy and cognitive dysfunction, ultimately leading to an inability to care for oneself. Although some pharmacologic treatments may alleviate AD symptoms, they do not halt the progression of AD and have multiple side effects. Based on the hypothesis that there are multiple pathogenic mechanisms in AD, and the progression of AD is affected by more than a single condition. Recently, the oxidative stress microenvironment in the brain has attracted much attention. Mesenchymal stem cells (MSCs) improve the microenvironment of the brain due to their multiple regulatory roles, such as immune regulation, anti-inflammation, regeneration, antioxidant, anti-apoptosis, and neuroprotection, which reduce pathological changes of AD and thus reduce its effects. MSCs, especially dental pulp stem cells (DPSCs) , not only secrete neuroprotective and anti- inflammatory factors to promote neuronal survival but also promote the accumulation of microglia around protein aggregates, remove pathological aggregates, and alleviate mitochondrial damage. This review focuses on using MSCs and potential MSCs cellular resources DPSCs to slow down AD development by improving the oxidative stress microenvironment, providing new ideas for treating AD in the clinic.

图1 阿尔茨海默病的危险因素
图2 AD的氧化应激机制注:ROS为活性氧,miRNA为微小核糖核酸;NOX为还原型烟酰胺腺嘌呤二核苷酸磷酸;Nrf2为核转录因子红细胞系2相关因子2 ;HO-1为血红素加氧酶1;AREs为抗氧化反应元件;Keap1为Kelch样ECH关联蛋白1;BDNF为脑源性神经营养因子;PI3K为磷脂酰肌醇3-激酶;AKT为丝氨酸/苏氨酸激酶;MEK为丝裂原活化蛋白激酶激酶;ERK为细胞外调节蛋白激酶;Molecile为分子;Cu2+/Fe2+/Zn2+为铜离子/铁离子/锌离子
图3 氧化应激与Aβ淀粉样蛋白间的关系注:AD为阿尔茨海默病;ROS为活性氧;・OH为羟自由基;Cu2+/Fe2+为铜离子/铁离子
图4 氧化应激与Tau蛋白异常磷酸化及神经炎症间的关系注:AD为阿尔茨海默病;NFTs为神经纤维缠结;TNF-α为肿瘤坏死因子;IL-6为白细胞介素6;IL-1β为白细胞介素1β
图5 MSCs诱导小胶质细胞表型变化
图6 DPSCs通过分泌多种细胞因子来调节受损的AD细胞模型,缓解神经毒性和维持神经突延伸,最终发挥神经保护作用注:VEGF为血管内皮生长因子;MCP-1为单核细胞趋化蛋白-1;CCL5为CCL5趋化因子;FRACTALKINE为Fractalkine趋化因子;SH-SY5Y为人神经母细胞瘤SH-SY5Y细胞;Aβ为β淀粉样蛋白;STZ为链脲佐菌素
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