人脐带间充质干细胞通过分泌IL-6介导冈田酸对SH-SY5Y细胞毒性的保护作用
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军事医学科学院输血医学研究所干细胞与再生医学研究室 广西医科大学,军事医学科学院输血医学研究所干细胞与再生医学研究室,军事医学科学院输血医学研究所干细胞与再生医学研究室,军事医学科学院输血医学研究所干细胞与再生医学研究室,军事医学科学院输血医学研究所干细胞与再生医学研究室

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国家高技术研究发展计划(2013AA020107),广州市健康医疗协同创新重大专项(201400000003),国家自然科学基金青年科学基金(81201611)和北京市科技新星计划(Z131102000413035)资助项目


IL-6 Mediates hUC-MSC Induced Recovery in Okadaic Acid Neurotoxicity of SH-SY5Y
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Stem Cell and Regenerative Medicine Laboratory,Beijing Institute of Transfusion Medicine Guangxi Medical College,Stem Cell and Regenerative Medicine Laboratory,Beijing Institute of Transfusion Medicine,Stem Cell and Regenerative Medicine Laboratory,Beijing Institute of Transfusion Medicine,Stem Cell and Regenerative Medicine Laboratory,Beijing Institute of Transfusion Medicine,Stem Cell and Regenerative Medicine Laboratory,Beijing Institute of Transfusion Medicine

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This work was supported by grants from Hi-Tech Research and Development Program of China (2013AA020107), Guangzhou City Health and Medical Cooperation Innovation Major Special(201400000003), Project of The National Natural Science Foundation of Youth Science Foundation(81201611) and Beijing New-star Plan of Science and Technology (Z131102000413035)

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    摘要:

    阿尔茨海默病(Alzheimer’s disease,AD)是一种国际公认的难治性神经退行性疾病,是引起痴呆的最常见的病因.其主要的病理学变化是由 Aβ过度沉积引起的老年斑(SP),以及 Tau蛋白过度磷酸化引起的神经纤维缠结(NFTs).从人脐带华通胶中分离出的间充质干细胞(hUC-MSCs)由于其强大的旁分泌作用,已经被证实对神经系统疾病有治疗效果,其中包括AD,这种治疗机制尚不明确.本研究用冈田酸对 SH-SY5Y 细胞系进行损伤,建立 AD 体外模型,然后用种有hUC-MSCs的transwell 小室或其条件培养基对模型进行治疗,并发现其分泌的IL-6可能是介导这种修复作用的关键因子.

    Abstract:

    Alzheimer's disease (AD) is currently an incurable neurodegenerative disease, which is the most common cause of dementia worldwide. AD is also a progressive disorder, pathologically characterized by extracellular amyloid beta plaques and intracellular neurofibrillary tangles (NFTs). NFTs consist of paired helical filaments of microtubule-associated tau protein that is hyperphosphorylated and the density of tau tangles correlates well with regional and global aspects of AD-associated cognitive dysfunction. Furthermore, the established toxic role of tau in certain genetic forms of frontotemporal dementia strongly suggests that tau aggregation may result in a toxic gain-of-function leading to the AD-associated neurodegeneration. Thus, there is a growing interest in discovering novel compounds that will help in reducing the deleterious accumulation of tau protein tangles in the AD brain. Stem cells treatment open a gate to this which many drugs show hard to control the disease progression or enhance the patients' consideration function. hUC-MSCs (mesenchymal stem cells isolated from human Wharton's jelly of unbilical cord), emphasized by its powerful paracrine, great function of multi-directional differentiation and east to isolate, have been confirmed effective to many nervous system disease including AD. But the treatment mechanism was still unknown. Along with the studies of secreted factors by hUC-MSCs, the paracrine function of the adult stem cells attracted us to answer this treatment mechanism from those star factors. Here, we set up the AD model in vitro by okadaic acid (OA), and demonstrate that IL-6 maybe the key protein to effect the recovery function of hUC-MSCs to protect the injured cells.

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翟晶磊,曹宁,岳文,贾雅丽,裴雪涛.人脐带间充质干细胞通过分泌IL-6介导冈田酸对SH-SY5Y细胞毒性的保护作用[J].生物化学与生物物理进展,2016,43(2):141-149

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历史
  • 收稿日期:2015-06-08
  • 最后修改日期:2015-12-23
  • 接受日期:2015-12-21
  • 在线发布日期: 2016-02-19
  • 出版日期: 2016-02-20