Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid- oligomers
Mesenchymal stem cells and cell-derived extracellular vesicles protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid- oligomers
复制标题
DOI：
10.1074/jbc.m117.807180
复制
发表时间：
2018-02-09
影响因子：
4.8
通讯作者：
Ferreira, Sergio T.
中科院分区：
文献类型：
--
作者：
de Godoy, Mariana A.;Saraiva, Leonardo M.;Ferreira, Sergio T.
阿尔茨海默病（AD）是一种致残性和高度流行的神经退行性疾病，目前尚无有效的治疗方法。淀粉样肽（AO）的可溶性寡聚体被认为是参与早期神经元氧化应激和突触损伤的近端神经毒素，最终导致AD中的神经变性和记忆障碍。本研究的目的是评估间充质干细胞（MSC）对海马神经元的有害影响的神经保护潜力。为此，我们建立了大鼠海马神经元和MSC的transwell共培养。我们发现，MSC和MSC衍生的细胞外囊泡保护神经元免受AO诱导的氧化应激和突触损伤，揭示了突触前和突触后标志物的损失。MSC的保护需要三种互补机制：1）AO的内化和降解; 2）含有活性过氧化氢酶的细胞外囊泡的释放;和3）白介素-6、白介素-10和血管内皮生长因子选择性分泌到培养基中。结果支持的概念，骨髓间充质干细胞可能是一个有前途的替代细胞为基础的治疗AD。
Alzheimer's disease (AD) is a disabling and highly prevalent neurodegenerative condition, for which there are no effective therapies. Soluble oligomers of the amyloid- peptide (AOs) are thought to be proximal neurotoxins involved in early neuronal oxidative stress and synapse damage, ultimately leading to neurodegeneration and memory impairment in AD. The aim of the current study was to evaluate the neuroprotective potential of mesenchymal stem cells (MSCs) against the deleterious impact of AOs on hippocampal neurons. To this end, we established transwell cocultures of rat hippocampal neurons and MSCs. We show that MSCs and MSC-derived extracellular vesicles protect neurons against AO-induced oxidative stress and synapse damage, revealed by loss of pre- and postsynaptic markers. Protection by MSCs entails three complementary mechanisms: 1) internalization and degradation of AOs; 2) release of extracellular vesicles containing active catalase; and 3) selective secretion of interleukin-6, interleukin-10, and vascular endothelial growth factor to the medium. Results support the notion that MSCs may represent a promising alternative for cell-based therapies in AD.