scholarly journals 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

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1059 ◽  
Author(s):  
Chiara A. Elia ◽  
Matteo Tamborini ◽  
Marco Rasile ◽  
Genni Desiato ◽  
Sara Marchetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Clinical Manifestations ◽  
Plaque Burden ◽  
Intracerebral Injection ◽  
Early Stages ◽  
Β Amyloid

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.

Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer’s disease evaluated by β-amyloid positron emission tomography imaging

2020 ◽  
Vol 54 (9) ◽  
pp. 883-891
Author(s):  
Bok-Nam Park ◽  
Jang-Hee Kim ◽  
Tae Sung Lim ◽  
So Hyun Park ◽  
Tae-Gyu Kim ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Positron Emission Tomography ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Standardized Uptake Value ◽  
Emission Tomography ◽  
Positron Emission ◽  
Β Amyloid

Objective: We evaluated the effects of bone marrow–derived mesenchymal stem cells in a model of Alzheimer’s disease using serial [18F]Florbetaben positron emission tomography. Methods: 3xTg Alzheimer’s disease mice were treated with intravenously injected bone marrow–derived mesenchymal stem cells, and animals without stem cell therapy were used as controls. Serial [18F]Florbetaben positron emission tomography was performed after therapy. The standardized uptake value ratio was measured as the cortex standardized uptake value divided by the cerebellum standardized uptake value. Memory function and histological changes were observed using the Barnes maze test and β-amyloid-reactive cells. Results: Standardized uptake value ratio decreased significantly from day 14 after stem cell administration in the bone marrow–derived mesenchymal stem cells–treated group ( n = 28). In contrast, there was no change in the ratio in control mice ( n = 25) at any time point. In addition, mice that received bone marrow–derived mesenchymal stem cell therapy also exhibited significantly better memory function and less β-amyloid-immunopositive plaques compared to controls. Conclusion: The therapeutic effect of intravenously injected bone marrow–derived mesenchymal stem cells in a mouse model of Alzheimer’s disease was confirmed by β-amyloid positron emission tomography imaging, memory functional studies and histopathological evaluation.

P1-162: Neuroprotective Effect of Extracellular Vesicles Derived From Mesenchymal Stem Cells in a Model of Alzheimer's Disease

2016 ◽  
Vol 12 ◽  
pp. P464-P465
Author(s):  
Luiza Carvalho ◽  
Mariana Araya de Godoy ◽  
Leonardo Martins Saraiva ◽  
Victor Bodart ◽  
Rafael Soares ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Neuroprotective Effect ◽  
Model Of Alzheimer’S Disease

scholarly journals 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

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Victor Bodart-Santos ◽  
Luiza R. P. de Carvalho ◽  
Mariana A. de Godoy ◽  
André F. Batista ◽  
Leonardo M. Saraiva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Extracellular Vesicles ◽  
Hippocampal Neurons ◽  
Neuronal Damage ◽  
Wharton’S Jelly ◽  
Wharton's Jelly

Abstract 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 (AβOs). 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 AβOs. Results hMSC-EVs were internalized by hippocampal cells in culture, and this was enhanced in the presence of AβOs in the medium. hMSC-EVs protected hippocampal neurons from oxidative stress and synapse damage induced by AβOs. 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 AβOs, 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.

scholarly journals Mesenchymal stem cells: As a multi-target cell therapy for clearing β-amyloid deposition in Alzheimer’s disease

BIOCELL ◽  
2022 ◽  
Vol 46 (3) ◽  
pp. 583-592
Author(s):  
RUXIN ZHANG ◽  
CHENGGANG LI ◽  
RUOCHEN DU ◽  
YITONG YUAN ◽  
BICHUN ZHAO ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Target Cell ◽  
Amyloid Deposition ◽  
Β Amyloid
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