Extracellular vesicles derived from human Wharton's jelly mesenchymal stem cells protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-β oligomers

被引：109

作者：

Bodart-Santos, Victor ^{[1
,2
,3
]}

de Carvalho, Luiza R. P. ^{[1
]}

de Godoy, Mariana A. ^{[1
,2
]}

Batista, Andre F. ^{[2
]}

Saraiva, Leonardo M. ^{[2
]}

Lima, Luize G. ^{[4
]}

Abreu, Carla Andreia ^{[1
]}

De Felice, Fernanda G. ^{[2
,5
,6
]}

Galina, Antonio ^{[2
]}

Mendez-Otero, Rosalia ^{[1
,7
]}

Ferreira, Sergio T. ^{[1
,2
]}

机构：

[1] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, BR-21941902 Rio De Janeiro, RJ, Brazil

[2] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, BR-21941902 Rio De Janeiro, RJ, Brazil

[3] Univ Fed Rio de Janeiro, Inst Biomed Sci, BR-21941902 Rio De Janeiro, RJ, Brazil

[4] Natl Canc Inst, BR-20230240 Rio De Janeiro, RJ, Brazil

[5] Queens Univ, Ctr Neurosci Studies, Kingston, ON K7L 3N6, Canada

[6] Queens Univ, Dept Psychiat, Kingston, ON K7L 3N6, Canada

[7] Natl Inst Sci & Technol Regenerat Med, BR-21941590 Rio De Janeiro, RJ, Brazil

来源：

STEM CELL RESEARCH & THERAPY | 2019年 / 10卷 / 01期

关键词：

AMYOTROPHIC-LATERAL-SCLEROSIS; A-BETA; ALZHEIMERS-DISEASE; STROMAL CELLS; MITOCHONDRIAL DYSFUNCTION; NEUROVASCULAR PLASTICITY; FUNCTIONAL RECOVERY; MEMORY LOSS; EXOSOMES; BRAIN;

D O I：

10.1186/s13287-019-1432-5

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Background Mesenchymal stem cells (MSCs) have been explored as promising tools for treatment of several neurological and neurodegenerative diseases. MSCs release abundant extracellular vesicles (EVs) containing a variety of biomolecules, including mRNAs, miRNAs, and proteins. We hypothesized that EVs derived from human Wharton's jelly would act as mediators of the communication between hMSCs and neurons and could protect hippocampal neurons from damage induced by Alzheimer's disease-linked amyloid beta oligomers (A beta Os). Methods We isolated and characterized EVs released by human Wharton's jelly mesenchymal stem cells (hMSC-EVs). The neuroprotective action of hMSC-EVs was investigated in primary hippocampal cultures exposed to A beta Os. Results hMSC-EVs were internalized by hippocampal cells in culture, and this was enhanced in the presence of A beta Os in the medium. hMSC-EVs protected hippocampal neurons from oxidative stress and synapse damage induced by A beta Os. Neuroprotection by hMSC-EVs was mediated by catalase and was abolished in the presence of the catalase inhibitor, aminotriazole. Conclusions hMSC-EVs protected hippocampal neurons from damage induced by A beta Os, and this was related to the transfer of enzymatically active catalase contained in EVs. Results suggest that hMSC-EVs should be further explored as a cell-free therapeutic approach to prevent neuronal damage in Alzheimer's disease.

引用

页数：13

共 94 条

[81] Human Mesenchymal Stem Cells Efficiently Manage Oxidative Stress [J].