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

Chen, Yi‐An; Lu, Cheng-Hsiu; Ke, Chien-Chih; Liu, Ren-Shyan

doi:10.3390/membranes11100796

Cited by 16 publications

(9 citation statements)

References 139 publications

(149 reference statements)

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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%

“…To be fully comprehensive, however, the results obtained should be analyzed by clinical trials [ 83 , 87 , 88 ]. Due to the paucity of standard protocols and mechanisms available for the procedures, the development of MSC-EV-dependent therapies has been challenged [ 89 , 90 ]. It should be mentioned, however, that some such properties, in particular the drug accumulation within MSC-EVs, have been approved for specific targeting according to recent technical advances [ 91 , 92 ].…”

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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“…These substances can be secreted and transferred to other cells or used to control the surrounding microenvironment. Exosomes can be transferred to target cells through the BBB without being degraded in blood because they are surrounded by lipid bilayer (Chen et al, 2021). Recently, an exosome-based mesenchymal stem cell trial is launched in China.…”

Section: Proposed Mechanisms Of Action Of Mesenchymal Stem Cells Ther...mentioning

confidence: 99%

Alzheimer’s Disease: From Pathogenesis to Mesenchymal Stem Cell Therapy – Bridging the Missing Link

Wang

2022

Front. Cell. Neurosci.

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Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease worldwide. With the increasing trend of population aging, the estimated number of AD continues to climb, causing enormous medical, social and economic burden to the society. Currently, no drug is available to cure the disease or slow down its progression. There is an urgent need to improve our understanding on the pathogenesis of AD and develop novel therapy to combat it. Despite the two well-known pathological hallmarks (extracellular amyloid plaques and intracellular Neurofibrillary Tangles), the exact mechanisms for selective degeneration and loss of neurons and synapses in AD remain to be elucidated. Cumulative studies have shown neuroinflammation plays a central role in pathogenesis of AD. Neuroinflammation is actively involved both in the onset and the subsequent progression of AD. Microglia are the central player in AD neuroinflammation. In this review, we first introduced the different theories proposed for the pathogenesis of AD, focusing on neuroinflammation, especially on microglia, systemic inflammation, and peripheral and central immune system crosstalk. We explored the possible mechanisms of action of stem cell therapy, which is the only treatment modality so far that has pleiotropic effects and can target multiple mechanisms in AD. Mesenchymal stem cells are currently the most widely used stem cell type in AD clinical trials. We summarized the ongoing major mesenchymal stem cell clinical trials in AD and showed how translational stem cell therapy is bridging the gap between basic science and clinical intervention in this devastating disorder.

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“…Although there are numerous clinical trials on the use of MSCs in the treatment of liver disease, to date, no clinical trials have been performed on the use of MSC-EVs despite their benefits. However, it has been used to treat many disorders, including orthopaedic disease ( 151 ), neurodegenerative disease ( 183 ), myocardial disease ( 184 ), renal disease, graft versus host disease (GvHD), pancreatic cancer and type 1 diabetes and has shown promising results ( 185 ). Despite the therapeutic potential of MSC-EVs and their beneficial effects in preclinical studies, several issues related to the clinical use of these vesicles remain unresolved.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Mesenchymal Stromal/Stem Cells and Their Extracellular Vesicles Application in Acute and Chronic Inflammatory Liver Diseases: Emphasizing on the Anti-Fibrotic and Immunomodulatory Mechanisms

et al. 2022

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Various factors, including viral and bacterial infections, autoimmune responses, diabetes, drugs, alcohol abuse, and fat deposition, can damage liver tissue and impair its function. These factors affect the liver tissue and lead to acute and chronic liver damage, and if left untreated, can eventually lead to cirrhosis, fibrosis, and liver carcinoma. The main treatment for these disorders is liver transplantation. Still, given the few tissue donors, problems with tissue rejection, immunosuppression caused by medications taken while receiving tissue, and the high cost of transplantation, liver transplantation have been limited. Therefore, finding alternative treatments that do not have the mentioned problems is significant. Cell therapy is one of the treatments that has received a lot of attention today. Hepatocytes and mesenchymal stromal/stem cells (MSCs) are used in many patients to treat liver-related diseases. In the meantime, the use of mesenchymal stem cells has been studied more than other cells due to their favourable characteristics and has reduced the need for liver transplantation. These cells increase the regeneration and repair of liver tissue through various mechanisms, including migration to the site of liver injury, differentiation into liver cells, production of extracellular vesicles (EVs), secretion of various growth factors, and regulation of the immune system. Notably, cell therapy is not entirely excellent and has problems such as cell rejection, undesirable differentiation, accumulation in unwanted locations, and potential tumorigenesis. Therefore, the application of MSCs derived EVs, including exosomes, can help treat liver disease and prevent its progression. Exosomes can prevent apoptosis and induce proliferation by transferring different cargos to the target cell. In addition, these vesicles have been shown to transport hepatocyte growth factor (HGF) and can promote the hepatocytes’(one of the most important cells in the liver parenchyma) growths.

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

Cited by 16 publications

References 139 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

Alzheimer’s Disease: From Pathogenesis to Mesenchymal Stem Cell Therapy – Bridging the Missing Link

Mesenchymal Stromal/Stem Cells and Their Extracellular Vesicles Application in Acute and Chronic Inflammatory Liver Diseases: Emphasizing on the Anti-Fibrotic and Immunomodulatory Mechanisms

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