中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2019, Vol. 14 ›› Issue (9): 1626-1634.doi: 10.4103/1673-5374.255978

• 原著:退行性病与再生 • 上一篇    下一篇

间充质干细胞源性外泌体促进阿尔茨海默病小鼠神经发生和认知功能恢复

  

  • 出版日期:2019-09-15 发布日期:2019-09-15
  • 基金资助:

    CONACYT奖学金＃487713和哈利斯科州混合科学技术基金JAL-2014-0-250508资助

Mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

Edwin E. Reza-Zaldivar 1 , Mercedes A. Hernández-Sapiéns 1 , Yanet K. Gutiérrez-Mercado 1 , Sergio Sandoval-Ávila 1 , Ulises Gomez-Pinedo 2 , Ana L. Márquez-Aguirre 1 , Estefanía Vázquez-Méndez 1 , Eduardo Padilla-Camberos 1 , Alejandro A. Canales-Aguirre 1   

  1. 1 Unidad de Evaluación Preclínica, Unidad de Biotecnología Médica y Farmacéutica, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco, Guadalajara, Mexico
    2 Regenerative Medicine Unit, Neuroscience Institute, Department of Neurosurgery and Neurology, IdISSC Health Research Institute of the Hospital Clínico San Carlos, Madrid, Spain
  • Online:2019-09-15 Published:2019-09-15
  • Contact: Alejandro A. Canales-Aguirre, acanales@ciatej.mx.
  • Supported by:

    The present work was sponsored by CONACYT scholarship #487713 and by Fondo Mixto de Ciencia y Tecnología del Estado de Jalisco grant JAL-2014-0-250508.

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摘要：

已有研究显示，间充质干细胞衍生的外泌体可以增强神经可塑性和改善认知障碍，为评估间充质干细胞源性外泌体对阿尔茨海默病小鼠神经发生和认知能力的影响，实验将β淀粉样蛋白1-42注射于小鼠双侧海马齿状回建立阿尔茨海默病小鼠模型,分别随机于小鼠齿状回中注射间充质干细胞或间充质干细胞源性外泌体。14和28天后，通过Morris水迷宫和异常物体识别测试评估小鼠认知能力。接下来，以免疫荧光测定小鼠脑室下区反映神经发生的双皮质素和PSA-NCAM的免疫反应。实验发现间充质干细胞源性外泌体可刺激脑室下区的神经发生，并减轻由β淀粉样蛋白诱导的认知障碍，该效果与间充质干细胞作用类似。实验结果为开发阿尔茨海默病的无细胞治疗策略提供了可能性。实验于2016年4月25日经动物伦理委员会（CICUAL 2016-011）批准。

orcid: 0000-0003-0918-788X (Alejandro A. Canales-Aguirre)

关键词: 阿尔茨海默病, 神经退行性疾病, 认知障碍, 记忆, AD小鼠模型, 间充质干细胞, 外来体, 神经发生, 认知改善, 无细胞疗法

Abstract:

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment. The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease. Alzheimer’s disease mouse models were established by injection of beta amyloid 1−42 aggregates into dentate gyrus bilaterally. Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration. Afterwards, neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies. Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1−42-induced cognitive impairment, and these effects are similar to those shown in the mesenchymal stem cells. These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease. All procedures and experiments were approved by Institutional Animal Care and Use Committee (CICUAL) (approval No. CICUAL 2016-011) on April 25, 2016.

Key words: Alzheimer’s disease, neurodegenerative disease, cognitive impairment, memory, Alzheimer’s disease mouse model, mesenchymal stem cell, exosomes, neurogenesis, cognitive improvement, cell-free therapy, neural regeneration