Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease.
Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease.
复制标题
在阿尔茨海默氏病鼠模型的海马中，VEGF过表达的VEGF过表达骨髓间充质干细胞的治疗作用。
DOI：
10.3389/fnagi.2014.00030
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发表时间：
2014
影响因子：
4.8
通讯作者：
Longo BM
中科院分区：
文献类型：
--
作者：
Garcia KO;Ornellas FL;Martin PK;Patti CL;Mello LE;Frussa-Filho R;Han SW;Longo BM
阿尔茨海默病 (AD) 的临床特征是进行性记忆丧失、行为和学习功能障碍以及认知缺陷，例如社交互动的改变。 AD的主要病理特征是老年斑和神经原纤维缠结的形成以及神经元和血管损伤。带有 APPswe/PS1dE9 突变的 AD 双转基因小鼠模型 (2xTg-AD) 显示出与 AD 患者中观察到的特征相似的特征，包括社会记忆障碍、老年斑形成和血管缺陷。当间充质干细胞 (MSC) 移植到大脑中时，可通过减少转基因淀粉样前体蛋白 (APP)/早老素 1 (PS1) 小鼠中淀粉样蛋白 -β (Aβ) 的沉积来产生积极作用。血管内皮生长因子 (VEGF) 对 AD 神经变性中涉及的兴奋性毒性具有神经保护作用。本研究探讨了过度表达 VEGF 的 MSC 对 2xTg-AD 转基因小鼠海马新生血管形成、认知功能障碍和老年斑的影响。通过电穿孔，用克隆在 uP 载体中、在修饰的 CMV 启动子 (uP-VEGF) 载体控制下的血管内皮生长因子转染 MSC，并在第 14 代扩增。将 MSC-VEGF 或 MSC 移植到 6、9 和 12 个月大的 2xTg-AD 动物中。这些动物接受了行为任务测试，包括运动、新奇探索、学习和记忆，并通过免疫组织化学 (IHC) 分析了它们大脑的血管化和 Aβ 斑块。 MSC-VEGF 治疗有利于海马特定层的新血管形成并减少老年斑。因此，通过恢复对新奇事物的天生兴趣并抵消这些 AD 转基因动物中存在的记忆缺陷，该治疗能够提供行为益处并减少认知缺陷。因此，这项研究对于AD引起的神经变性中的血管损伤具有重要的治疗意义。
Alzheimer’s disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. The major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. The double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (Aβ) deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. The present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. The animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and Aβ plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD.
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影响因子：
3.7
作者：
Bories C;Guitton MJ;Julien C;Tremblay C;Vandal M;Msaid M;De Koninck Y;Calon F
通讯作者：
Calon F
影响因子：
168.9
作者：
Cagnin, A;Brooks, DJ;Banati, RB
通讯作者：
Banati, RB
影响因子：
56.9
作者：
Brazelton, TR;Rossi, FMV;Blau, HM
通讯作者：
Blau, HM
DOI：
10.1016/j.bbrc.2007.01.045
发表时间：
2007-03-16
影响因子：
3.1
作者：
Iso, Yoshitaka;Spees, Jeffrey L.;Prockop, Darwin J.
通讯作者：
Prockop, Darwin J.
影响因子：
9.3
作者：
Bertram, L;Tanzi, RE
通讯作者：
Tanzi, RE