期刊
CELLS
卷 8, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cells8091059
关键词
bone marrow mesenchymal stem cells; extracellular vesicles; Alzheimer's disease; APPswe; PS1dE9 AD mice; Neprilysin; dystrophic neuritis; SMI; A beta plaques
类别
资金
- Regione Lombardia NeOn, POR-FESR 2014-2020 [239047, CUP E47F17000000009, CUP_B42F16000440005, Cariplo 2015-0594]
- Fondazione Pisa [107/16]
Bone marrow Mesenchymal Stem Cells (BM-MSCs), due to their strong protective and anti-inflammatory abilities, have been widely investigated in the context of several diseases for their possible therapeutic role, based on the release of a highly proactive secretome composed of soluble factors and Extracellular Vesicles (EVs). BM-MSC-EVs, in particular, convey many of the beneficial features of parental cells, including direct and indirect beta-amyloid degrading-activities, immunoregulatory and neurotrophic abilities. Therefore, EVs represent an extremely attractive tool for therapeutic purposes in neurodegenerative diseases, including Alzheimer's disease (AD). We examined the therapeutic potential of BM-MSC-EVs injected intracerebrally into the neocortex of APPswe/PS1dE9 AD mice at 3 and 5 months of age, a time window in which the cognitive behavioral phenotype is not yet detectable or has just started to appear. We demonstrate that BM-MSC-EVs are effective at reducing the A beta plaque burden and the amount of dystrophic neurites in both the cortex and hippocampus. The presence of Neprilysin on BM-MSC-EVs, opens the possibility of a direct beta-amyloid degrading action. Our results indicate a potential role for BM-MSC-EVs already in the early stages of AD, suggesting the possibility of intervening before overt clinical manifestations.
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