Mesenchymal stem cell-derived extracellular vesicles: a glimmer of hope in treating Alzheimer’s disease

Liew, Lee Chuen; Katsuda, Takeshi; Gailhouste, Luc; Nakagama, Hitoshi; Ochiya, Takahiro

doi:10.1093/intimm/dxx002

Cited by 78 publications

(52 citation statements)

References 112 publications

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“…Extensive investigations have shown that MSCs can cross the blood-brain barrier via intracerebral (transplantation into hippocampus or lateral ventricles), intracarotid, or intravenous injections (Lo Furno et al, 2017 ). These cells and their extracellular vesicles could stimulate neurogenesis (Oh et al, 2015 ) and could significantly rescue learning and memory deficits of animals with Aβ deposition reduction and modification of size and number of microglial cells (Duncan and Valenzuela, 2017 ; Liew et al, 2017 ). However, MSCs have a low survival rate after transplanted due to the adverse microenvironment [i.e., presence of cytotoxic Aβ oligomers and p-tau, and increased reactive oxygen species (ROS)] (Lee et al, 2015 ; Oh et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model

et al. 2018

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Widespread death of transplanted mesenchymal stem cells (MSCs) hampers the development of stem cell therapy for Alzheimer disease (AD). Cell pre-conditioning might help cope with this challenge. We tested whether let-7f-5p-modified MSCs could prolong the survival of MSCs after transplantation. When exposed to Aβ25−35 in vitro, MSCs showed significant early apoptosis with decrease in the let-7f-5p levels and increased caspase-3 expression. Upregulating microRNA let-7f-5p in MSCs alleviated Aβ25−35-induced apoptosis by decreasing the caspase-3 levels. After computerized analysis and the luciferase reporter assay, we identified that caspases-3 was the target gene of let-7f-5p. In vivo, hematoxylin and eosin staining confirmed the success of MSCs transplantation into the lateral ventricles, and the let-7f-5p upregulation group showed the lowest apoptotic rate of MSCs detected by TUNEL immunohistochemistry analysis and immunofluorescence. Similarly, bioluminescent imaging showed that let-7f-5p upregulation moderately prolonged the retention of MSCs in brain. In summary, we identified the anti-apoptotic role of let-7f-5p in Aβ25−35-induced cytotoxicity, as well as the protective effect of let-7f-5p on survival of grafted MSCs by targeting caspase-3 in AD models. These findings show a promising approach of microRNA-modified MSCs transplantation as a therapy for neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%

MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model

et al. 2018

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“…Significant research is still required in order to guarantee the long-term biological safety of these exosomes, and confirm the potential adverse effects and efficacy of exosome administration in patients with AD. 114 We also need to know more about the time of administration, the most effective route of administration, including dose-response experiments, before considering MSC-derived exosomes for clinical application.…”

Section: Challenges and Limitationsmentioning

confidence: 99%

<p>Targetting Exosomes as a New Biomarker and Therapeutic Approach for Alzheimer’s Disease</p>

Yin

et al. 2020

CIA

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Alzheimer's disease (AD) is a neurodegenerative disease that mainly occurs in old age and involves progressive cognitive impairment. AD has become a major global issue for public health, with approximately 24 million people currently affected by the disease. Estimates indicted that this number will quadruple by 2050. Because of the high incidence of AD, there is an urgent need to develop new strategies to diagnose and treat AD. Many recent studies have indicated the multiple, yet somewhat controversial, roles of exosomes in AD. Although the underlying mechanisms by which exosomes play a role in AD are still unknown, current evidence suggests that exosomes can carry and spread toxic amyloid-beta, and hyperphosphorylated tau, between cells, and then induce apoptosis, thus contributing to the loss of neurons. In addition, exosomes appear to possess the ability to reduce brain amyloid-beta, and tau hyperphosphorylation, and transfer neuroprotective substances between neural cells. The accumulating data brings hope that the application of exosomes may be helpful for early diagnostics and the identification of new therapeutic targets for AD. Here, we summarized the various roles of exosomes, and how they might relate to the pathogenesis of AD. We also highlight the potential application of exosomes as a therapeutic option in AD therapy.

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“…The exosomes and microvesicles released from modified MSCs are enriched in factors of interest to enhance the therapeutic effects. Overexpression of Aβ degrading enzymes or downregulation of secretase enzymes related to Aβ formation with transfecting different RNAs can be useful in ameliorating disease symptoms (153). Brn-4 protein in MSCs can inhibit the accumulation of Aβ in the brain but miR-937 presence impedes the translation of Brn-4 mRNA to protein.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

Sadatpoor

Salehi

Rahban

et al. 2020

IJSC

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Mesenchymal stem cells (MSCs) are multipotent stem cells that have multilinear differentiation and self-renewal abilities. These cells are immune-privileged as they express no or low level of class-II major histocompatibility complex (MHC-II) and other costimulatory molecules. Having neuroprotective and regenerative properties, MSCs can be used to ameliorate several intractable neurodegenerative disorders by affecting both innate and adaptive immune systems. Several manipulations like pretreating MSCs with different conditions or agents, and using molecules derived from MSCs or genetically manipulating them, are the common and practical ways that can be used to strengthen MSCs survival and potency. Improved MSCs can have significantly enhanced impacts on diseases compared to MSCs not manipulated. In this review, we describe some of the most important manipulations that have been exerted on MSCs to improve their therapeutic functions and their applications in ameliorating three prevalent neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease.

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Mesenchymal stem cell-derived extracellular vesicles: a glimmer of hope in treating Alzheimer’s disease

Cited by 78 publications

References 112 publications

MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model

MicroRNA Let-7f-5p Promotes Bone Marrow Mesenchymal Stem Cells Survival by Targeting Caspase-3 in Alzheimer Disease Model

<p>Targetting Exosomes as a New Biomarker and Therapeutic Approach for Alzheimer’s Disease</p>

Manipulated Mesenchymal Stem Cells Applications in Neurodegenerative Diseases

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