Mesenchymal stem cells-derived extracellular vesicles ameliorate Alzheimer’s disease in rat models via the microRNA-29c-3p/BACE1 axis and the Wnt/β-catenin pathway

Sha, Sha; Shen, Xueli; Cao, Yunpeng; Qu, Le

doi:10.18632/aging.203088

Cited by 58 publications

(44 citation statements)

References 68 publications

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“…Combinations of this type had been previously hypothesized for BACE-1, however, a few years ago [ 100 ]. At present, the MSC-EVs in various properties [ 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 ], in drug delivery [ 91 , 92 ], and in combined employment through a miRNA-BACE-1 axis and various pathways addressed to β-catenin [ 81 , 82 ], have yielded very encouraging results. The new findings concerning MSC-EVs and their therapy agents, considered also in their possible combinations as mentioned here, confirm the improvement of AD therapy, with substantial advantage for the whole population of patients, existing already now and with improvement expected in the next few years.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the therapeutic effects of MSC-EVs do not depend only on the whole vesicles. Rather, their released cargo miRNAs induce inhibition of BACE-1 expression and activation of intracellular signaling cascades, such as those operative along the Wnt/β-catenin and the AKT/GSK-3β/β-catenin pathways [ 81 , 82 ]. Therefore, the mechanisms of MSC-EV action appear more complex than previously proposed.…”

Section: Present Therapies For Alzheimer’s Diseasementioning

confidence: 99%

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News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

Meldolesi

2022

Biomedicines

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Upon its discovery, Alzheimer’s, the neurodegenerative disease that affects many millions of patients in the world, remained without an effective therapy. The first drugs, made available near the end of last century, induced some effects, which remained only marginal. More promising effects are now present, induced by two approaches. Blockers of the enzyme BACE-1 induce, in neurons and glial cells, decreased levels of Aβ, the key peptide of the Alzheimer’s disease. If administered at early AD steps, the BACE-1 blockers preclude further development of the disease. However, they have no effect on established, irreversible lesions. The extracellular vesicles secreted by mesenchymal stem cells induce therapy effects analogous, but more convenient, than the effects of their original cells. After their specific fusion to target cells, the action of these vesicles depends on their ensuing release of cargo molecules, such as proteins and many miRNAs, active primarily on the cell cytoplasm. Operationally, these vesicles exhibit numerous advantages: they exclude, by their accurate selection, the heterogeneity of the original cells; exhibit molecular specificity due to their engineering and drug accumulation; and induce effective actions, mediated by variable concentrations of factors and molecules and by activation of signaling cascades. Their strength is reinforced by their combination with various factors and processes. The recent molecular and operations changes, induced especially by the stem cell target cells, result in encouraging and important improvement of the disease. Their further development is expected in the near future.

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Section: Discussionmentioning

confidence: 99%

Section: Present Therapies For Alzheimer’s Diseasementioning

confidence: 99%

News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

Meldolesi

2022

Biomedicines

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“…Transfection of BM-MSCs with the mir-17-92 cluster enriched their Evs and improved the tissue and functional behavior of rats subjected to a brain-injury model (Zhang Y. et al, 2021 ). Silencing mir-29c-3p also reduced the effect of BM-MSC-derived Evs in an AD model (Sha et al, 2021 ). The miR-125a found in BM-MSCs promotes M2 macrophage polarization, which was attenuated by the knockdown of this miRNA (Chang et al, 2021 ).…”

Section: Msc-derived Exosomes and Extracellular Vesicles (Evs)mentioning

confidence: 99%

Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases

Soares

Gonçalves

Vasques

et al. 2022

Front. Mol. Neurosci.

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Neurological disorders include a wide spectrum of clinical conditions affecting the central and peripheral nervous systems. For these conditions, which affect hundreds of millions of people worldwide, generally limited or no treatments are available, and cell-based therapies have been intensively investigated in preclinical and clinical studies. Among the available cell types, mesenchymal stem/stromal cells (MSCs) have been widely studied but as yet no cell-based treatment exists for neurological disease. We review current knowledge of the therapeutic potential of MSC-based therapies for neurological diseases, as well as possible mechanisms of action that may be explored to hasten the development of new and effective treatments. We also discuss the challenges for culture conditions, quality control, and the development of potency tests, aiming to generate more efficient cell therapy products for neurological disorders.

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“…In our study, WJ-MSCs-derived EVs also expressed active NEP on their membranes by means of Western blot and NEP-specific activity assay [ 71 ]. Furthermore, MSCs-derived EVs-treated AD rodent models exhibited elevated NEP and IDE expressions along with decreased Aβ depositions [ 85 , 92 ]. Taken together, these reports have demonstrated the potential of MSCs-derived EVs in the treatment of AD and further reflect the feasibility to lower brain Aβ levels by delivering NEP or other Aβ-degrading enzymes.…”

Section: Therapeutic Mechanisms Of Msc-derived Evs Actions In Admentioning

confidence: 99%

“…In a similar manner, BM-MSC-derived EVs were able to decrease iNOS expression in a model of osteoarthritis [ 110 ]. Additionally, levels of inflammatory cytokines, including IL-1β, IL-6 and TNF-α, were also decreased after MSC-derived EVs treatment [ 80 , 92 ].…”

Section: Therapeutic Mechanisms Of Msc-derived Evs Actions In Admentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapy for Alzheimer’s Disease: Progress and Opportunity

Chen

et al. 2021

Membranes

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Alzheimer’s disease (AD), as a neurodegenerative disorder, is characterized by mass neuronal and synaptic loss and, currently, there are no successful curative therapies. Extracellular vesicles (EVs) are an emerging approach to intercellular communication via transferring cellular materials such as proteins, lipids, mRNAs, and miRNAs from parental cells to recipient cells, leading to the reprogramming of the molecular machinery. Numerous studies have suggested the therapeutic potential of EVs derived from mesenchymal stem cells (MSCs) in the treatment of AD, based on the neuroprotective, regenerative and immunomodulatory effects as effective as MSCs. In this review, we focus on the biology and function of EVs, the potential of MSC-derived EVs for AD therapy in preclinical and clinical studies, as well as the potent mechanisms of MSC-derived EVs actions. Finally, we highlight the modification strategies and diagnosis utilities in order to make advance in this field.

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Mesenchymal stem cells-derived extracellular vesicles ameliorate Alzheimer’s disease in rat models via the microRNA-29c-3p/BACE1 axis and the Wnt/β-catenin pathway

Cited by 58 publications

References 68 publications

News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

News about Therapies of Alzheimer’s Disease: Extracellular Vesicles from Stem Cells Exhibit Advantages Compared to Other Treatments

Current Status of Mesenchymal Stem/Stromal Cells for Treatment of Neurological Diseases

Mesenchymal Stem Cell-Derived Extracellular Vesicle-Based Therapy for Alzheimer’s Disease: Progress and Opportunity

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