The effect of encapsulated VEGF-secreting cells on brain amyloid load and behavioral impairment in a mouse model of Alzheimer's disease

被引：112
作者：
Spuch, Carlos [1 ,2 ]
Antequera, Desiree [1 ,2 ]
Portero, Aitziber [3 ]
Drive, Gorka [3 ]
Hernandez, Rosa Ma [3 ]
Molina, Jose A. [2 ,4 ]
Bermejo-Pareja, Felix [2 ,4 ]
Pedraz, Jose L. [3 ]
Carro, Eva [1 ,2 ]
机构：
[1] Hosp 12 Octubre, Res Ctr, Neurosci Lab, E-28041 Madrid, Spain
[2] Neurodegenerat Dis Biomed Res Ctr CIBERNED, Madrid, Spain
[3] Univ Basque Country, Fac Pharm, Lab Pharm & Pharmaceut Technol, Vitoria, Spain
[4] Hosp 12 Octubre, Neurol Serv, E-28041 Madrid, Spain
来源：
BIOMATERIALS | 2010年 / 31卷 / 21期
关键词：
Angiogenesis; Animal model; Brain; Microencapsulation; Endothelial cells; ENDOTHELIAL GROWTH-FACTOR; VASCULAR DEMENTIA; TRANSGENIC MICE; BETA-PEPTIDE; NEURONS; NEURODEGENERATION; ANGIOGENESIS; CLEARANCE; RECEPTORS; TOXICITY;
D O I：
10.1016/j.biomaterials.2010.03.042
中图分类号：
R318 [生物医学工程];
学科分类号：
0831 ;
摘要：
Cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in Alzheimer's disease (AD). Vascular endothelial growth factor (VEGF), an angiogenic protein with important neurotrophic and neuroprotective actions, is under investigation as a therapeutic agent for the treatment of neurodegenerative disorders. The aim of this study was to generate encapsulated VEGF-secreting cells and implant them in a transgenic mouse model of AD, the double mutant amyloid precursor protein/presenilin 1 (APP/Ps1) mice, which shows a disturbed vessel homeostasis. We report that, after implantation of VEGF microcapsules, brain A beta burden, hyperphosphorylated-tau and cognitive impairment attenuated in APP/Ps1 mice. Based on the neurovascular hypothesis, our findings suggest a new potential therapeutic approach that could be developed for AD, to enhance A beta clearance and neurovascular repair, and to protect the cognitive behavior. Stereologically-implanted encapsulated VEGF-secreting cells could offer an alternative strategy in the treatment of AD. (c) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5608 / 5618
页数：11
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