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

Abstract

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.

Extracellular vesicles in neurodegenerative diseases: A systematic review

“…In total, 19 studies observed the pioneering role of EVs and exosomes as diagnostic biomarkers in neurodegenerative diseases ( Table 2 ; Coleman and Hill, 2015 ; Thompson et al, 2016 ; Vella et al, 2016 ; Barreca et al, 2017 ; Chen et al, 2017 ; Li et al, 2018 ; Pluta et al, 2018 ; Ramirez et al, 2018 ; Gámez-Valero et al, 2019 ; Karnati et al, 2019 ; Lee et al, 2019 ; Pluta and Ułamek-Kozioł, 2019 ; Pulliam et al, 2019 ; Vinaiphat and Sze, 2019 ; Banack et al, 2020 ; Guedes et al, 2020 ; Hornung et al, 2020 ; Rani et al, 2020 ; Leggio et al, 2021 ). Moreover, 14 studies alone demonstrated the therapeutic role of EVs and exosomes in neurodegenerative diseases ( Table 2 ; Kim et al, 2013 ; Katsuda et al, 2015 ; Rufino-Ramos et al, 2017 ; Sarko and McKinney, 2017 ; Araldi et al, 2020 ; Dolcetti et al, 2020 ; Lakshmi et al, 2020 ; Upadhya et al, 2020 ; Fayazi et al, 2021 ; Haney et al, 2021 ; Kumar et al, 2021 ; Reed and Escayg, 2021 ; Xu et al, 2021 ; Meldolesi, 2022 ). The overall risk biasness was visualized as demonstrated in Figures 4A,B (McGuinness and Higgins, 2021 ).…”

Engineered mesenchymal stem cell-derived extracellular vesicles: A state-of-the-art multifunctional weapon against Alzheimer's disease

“…The discovery that MSC therapies had serious problems led to studies on their secreted vesicles [81,85]. Several curative effects of MSCs have been recapitulated by MSC-EVs, which also leads to unexpected benefits, such as higher safety and tissue penetration [86]. Moreover, MSC-EVs are incapable of self-replicating, which prevents many risks of MSC therapy.…”

“…MiRs are noncoding RNAs closely related to AD pathogenesis and demonstrate enormous potential as therapeutic biomarkers [113]. Recent studies have demonstrated that BACE1 regulates AD progression via miRs [86,114]. Sha et al [97] discovered that miR-29c-3p delivered to neurons by bone marrow MSC-EVs (BMSC-EVs) inhibits BACE1 expression and activates the Wnt/β-catenin pathway to downregulate the level of BACE1 [115] and thereby exert a therapeutic effect on AD.…”

Extracellular vesicles and their cells of origin: Open issues in autoimmune diseases

“…These vesicles are involved in key innate and adaptive immunity processes, including but not limited to antigen presentation, inflammation, anti-microbial defence, development and activation of B- and T-cells, and allergic, autoimmune or anti-tumor responses ( 65 ). EVs have raised a good deal of promise for the efficient treatment of autoimmune diseases, as they carry the analogous advantages of their producer cells ( 66 ). While EVs from CD3+, activated CD8+, or engineered T-cells, natural killer cells, and M1 macrophages are mostly considered immune-active nano-vesicles, EVs from regulatory T-cells, MSCs, and M2 macrophages, as well as erythrocytes, neutrophils, platelets or cancerous cells are reported to have immunosuppressive features.…”