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

作　　者：Edwin E. Reza-Zaldivar Mercedes A. Hernández-Sapiéns Yanet K. Gutiérrez-Mercado Sergio Sandoval-ávila Ulises Gomez-Pinedo Ana L. Márquez-Aguirre Estefanía Vázquez-Méndez Eduardo Padilla-Camberos Alejandro A. Canales-Aguirre 

机构地区：[1]Unidad de Evaluation Preclinica,Unidad de Biotecnologia Medica y Farmaceutica,Centro de Investigation y Asistencia en Tecnologia y Diseno del Estado de Jalisco,Guadalajara,Mexico [2]Regenerative Medicine Unit,Neuroscience Institute,Department of Neurosurgery and Neurology,IdlSSC Health Research Institute of the Hospital Clinico San Carlos,Madrid,Spain

出　　处：《Neural Regeneration Research》2019年第9期1626-1634,共9页中国神经再生研究（英文版）

基　　金：sponsored by CONACYT scholarship#487713;Fondo Mixto de Ciencia y Tecnología del Estado de Jalisco grant JAL-2014-0-250508

摘　　要：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.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. CICUAL2016-011) on April 25, 2016.

关 键 词：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 

分 类 号：R456[医药卫生—治疗学] R361[医药卫生—临床医学]