Intracerebral Injection of Extracellular Vesicles from Mesenchymal Stem Cells Exerts Reduced Aβ Plaque Burden in Early Stages of a Preclinical Model of Alzheimer's Disease

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 Ext...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2019-09, Vol.8 (9), p.1059
Main Authors: Elia, Chiara A, Tamborini, Matteo, Rasile, Marco, Desiato, Genni, Marchetti, Sara, Swuec, Paolo, Mazzitelli, Sonia, Clemente, Francesca, Anselmo, Achille, Matteoli, Michela, Malosio, Maria Luisa, Coco, Silvia
Format: Article
Language:English
Subjects:
Alzheimer's disease
APPswe/PS1dE9 AD mice
Axons
Aβ plaques
Bone marrow
bone marrow mesenchymal stem cells
Cognitive ability
dystrophic neuritis
Extracellular vesicles
Immunoregulation
Inflammation
Mesenchymal stem cells
Neocortex
Neprilysin
Neurodegenerative diseases
Pathology
Peptides
Phenotypes
Potassium
Secretome
SMI
Software
Stem cell transplantation
Stem cells
Therapeutic applications
β-Amyloid
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Summary: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 β-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 Aβ 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 β-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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells8091059