Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes.
Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes.
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DOI：
10.1038/srep01197
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发表时间：
2013
影响因子：
4.6
通讯作者：
Ochiya, Takahiro
中科院分区：
文献类型：
--
作者：
Katsuda, Takeshi;Tsuchiya, Reiko;Kosaka, Nobuyoshi;Yoshioka, Yusuke;Takagaki, Kentaro;Oki, Katsuyuki;Takeshita, Fumitaka;Sakai, Yasuyuki;Kuroda, Masahiko;Ochiya, Takahiro
阿尔茨海默病（Alzheimer's disease，AD）是一种以β-淀粉样肽（β-amyloid peptide，Aβ）的产生和清除不平衡而导致Aβ在脑内蓄积为特征的疾病。脑啡肽酶（Neprilysin，NEP）是脑内最重要的Aβ降解酶。因此，研究人员已经探索了病毒介导的NEP基因递送。然而，这样的策略可能会带来意想不到的风险，因此还需要探索新的NEP交付的可能性。在这里，我们表明，人脂肪组织来源的间充质干细胞（ADSC）分泌携带酶活性NEP的外泌体。来自ADSC衍生的外泌体的1 μg蛋白的NEP比活性水平相当于约0.3ng重组人NEP的NEP比活性水平。 值得注意的是，ADSC衍生的外泌体被转移到N2 a细胞中，并被认为降低了N2 a细胞中的分泌和细胞内Aβ水平。重要的是，这些特征在ADSC中比骨髓来源的间充质干细胞更明显，表明ADSC来源的外泌体对AD的治疗相关性。
Alzheimer's disease (AD) is characterized by the accumulation of β-amyloid peptide (Aβ) in the brain because of an imbalance between Aβ production and clearance. Neprilysin (NEP) is the most important Aβ-degrading enzyme in the brain. Thus, researchers have explored virus-mediated NEP gene delivery. However, such strategies may entail unexpected risks, and thus exploration of a new possibility for NEP delivery is also required. Here, we show that human adipose tissue-derived mesenchymal stem cells (ADSCs) secrete exosomes carrying enzymatically active NEP. The NEP-specific activity level of 1 μg protein from ADSC-derived exosomes was equivalent to that of ~ 0.3 ng of recombinant human NEP. Of note, ADSC-derived exosomes were transferred into N2a cells, and were suggested to decrease both secreted and intracellular Aβ levels in the N2a cells. Importantly, these characteristics were more pronounced in ADSCs than bone marrow-derived mesenchymal stem cells, suggesting the therapeutic relevance of ADSC-derived exosomes for AD.
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影响因子：
46.9
作者：
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通讯作者：
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影响因子：
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通讯作者：
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