Systemic transplantation of human umbilical cord derived mesenchymal stem cells-educated T regulatory cells improved the impaired cognition in AβPPswe/PS1dE9 transgenic mice.
Systemic transplantation of human umbilical cord derived mesenchymal stem cells-educated T regulatory cells improved the impaired cognition in AβPPswe/PS1dE9 transgenic mice.
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DOI：
10.1371/journal.pone.0069129
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bi J
中科院分区：
文献类型：
--
作者：
Yang H;Yang H;Xie Z;Wei L;Bi J
阿尔茨海默病（Alzheimer's disease，AD）是最常见的痴呆之一，其特征是细胞外淀粉样β蛋白（amyloid-beta protein，Aβ）的沉积和神经元内神经元缠结的形成。立体定向间充质干细胞（mesenchymal stem cells，MSCs）作为免疫调节细胞移植到AD动物模型海马是预防AD进展的一种潜在治疗方法，但该方法具有创伤性，临床操作困难。全身和中枢神经系统炎症在AD的发病机制中起重要作用。调节性T细胞（Tlymphocytes，Tlymphocytes）在维持机体免疫稳态中起重要作用，提示Tlymphocytes移植可阻止炎症的进展。本研究旨在评价AβPPswe/PS1 dE 9双转基因小鼠经人脐带间充质干细胞（UC-MSCs）体外培养3 d后，从其脾脏中提取纯化的自体胸腺肽进行系统移植，是否能改善AβPPswe/PS1 dE 9双转基因小鼠的神经病理学和认知功能缺陷。我们观察到，自体THBE系统移植显著改善了受损的认知功能，减少了Aβ斑块沉积和可溶性Aβ水平，同时显著降低了活化的小胶质细胞和全身炎症因子水平。总之，自体TdR的系统移植可能是预防AD进展的有效且安全的干预措施。
Alzheimer’s disease (AD) is one of most prevalent dementias, which is characterized by the deposition of extracellular amyloid-beta protein (Aβ) and the formation of neurofibrillary tangles within neurons. Although stereotaxic transplantation of mesenchymal stem cells (MSCs) into the hippocampus of AD animal model as immunomodulatory cells has been suggested as a potential therapeutic approach to prevent the progress of AD, it is invasive and difficult for clinical perform. Systemic and central nervous system inflammation play an important role in pathogenesis of AD. T regulatory cells (Tregs) play a crucial role in maintaining systemic immune homeostasis, indicating that transplantation of Tregs could prevent the progress of the inflammation. In this study, we aimed to evaluate whether systemic transplantation of purified autologous Tregs from spleens of AβPPswe/PS1dE9 double-transgenic mice after MSCs from human umbilical cords (UC-MSCs) education in vitro for 3 days could improve the neuropathology and cognition deficits in AβPPswe/PS1dE9 double-transgenic mice. We observed that systemic transplantation of autologous Tregs significantly ameliorate the impaired cognition and reduced the Aβ plaque deposition and the levels of soluble Aβ, accompanied with significantly decreased levels of activated microglia and systemic inflammatory factors. In conclusion, systemic transplantation of autologous Tregs may be an effective and safe intervention to prevent the progress of AD.
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影响因子：
5.2
作者：
Romanov, YA;Svintsitskaya, VA;Smirnov, VN
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影响因子：
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