2020
DOI: 10.1038/s41598-020-67460-1
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Bone marrow-derived mesenchymal stem cells improve cognitive impairment in an Alzheimer’s disease model by increasing the expression of microRNA-146a in hippocampus

Abstract: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β and tau. We previously reported that administration of bone marrow mesenchymal stem cells (BM-MScs) ameliorates diabetes-induced cognitive impairment by transferring exosomes derived from these cells into astrocytes. Here, we show that intracerebroventricularly injected BM-MSCs improve cognitive impairment in AD model mice by ameliorating astrocytic inflammation as well as synaptogenesis. Although AD model mice showed an increase in NF-… Show more

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Cited by 135 publications
(117 citation statements)
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“…In line with these findings are results obtained by Nakano and colleagues, who emphasized the important role of MSC-sourced miRNA-146 for MSC-Exo-dependent suppression of microglia and neuroinflammation in AD mice [ 30 ]. MiRNA-146 is a small, noncoding RNA molecule, which regulates inflammatory properties of microglia [ 30 ].…”
Section: Therapeutic Effects Of Msc-exos In the Treatment Of Alzhesupporting
confidence: 74%
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“…In line with these findings are results obtained by Nakano and colleagues, who emphasized the important role of MSC-sourced miRNA-146 for MSC-Exo-dependent suppression of microglia and neuroinflammation in AD mice [ 30 ]. MiRNA-146 is a small, noncoding RNA molecule, which regulates inflammatory properties of microglia [ 30 ].…”
Section: Therapeutic Effects Of Msc-exos In the Treatment Of Alzhesupporting
confidence: 74%
“…In line with these findings are results obtained by Nakano and colleagues, who emphasized the important role of MSC-sourced miRNA-146 for MSC-Exo-dependent suppression of microglia and neuroinflammation in AD mice [ 30 ]. MiRNA-146 is a small, noncoding RNA molecule, which regulates inflammatory properties of microglia [ 30 ]. MSC-Exos, in miRna-146-dependent manner, inhibited TNF receptor-associated factor 6 (TRAF6) and IL-1 receptor-associated kinase 1 (IRAK1) in microglia, resulting in the down-regulated phosphorylation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) [ 30 ].…”
Section: Therapeutic Effects Of Msc-exos In the Treatment Of Alzhesupporting
confidence: 74%
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“…Recently, extracellular vesicles (EVs), such as exosomes and microvesicles, have been attracting a strong research interest for use as natural drug delivery systems ( Chen et al, 2018 ; Tang and Wang, 2020 ). Mesenchymal stem cell (MSC)-derived exosomes have been reported to be involved in multiple physiology and pathology activities including osteogenesis, bone regeneration, osteoarthritis, cardiomyoblast hypoxia–reperfusion, cognitive impairment, inflammation, stroke, sepsis, and tumorigenesis ( Zheng et al, 2018 ; Huang et al, 2020 ; Jin et al, 2020 ; Nakano et al, 2020 ; Tan et al, 2020 ; Venkat et al, 2020 ; Xu et al, 2020 ; Zou et al, 2020 ). Jia et al (2020) report that exosomes secreted by young MSCs promote osteogenesis and bone formation in older rats.…”
Section: Introductionmentioning
confidence: 99%
“…Similar results were also reported by Elia et al [ 150 ], who demonstrated that an intracerebral injection of extracellular vesicles from MSC exerts reduced Aβ plaque burden in early stages of a preclinical model of Alzheimer’s disease. The benefits of exosomal therapy were also reported by Nakano et al [ 151 ], who recently showed that the treatment of AD mouse model with BM-MSC-derived exosomes increased the expression of microRNA-146a in the hippocampus, decreasing the levels of nuclear factor kappa B (NF-κB) in astrocytes, leading to synaptogenesis and the correction of cognitive impairment. Furthermore, MSC-derived exosomes are also shown to suppress the inducible nitric oxide synthase (iNOS) in cultured primary neurons and ameliorate the neural impairment of CA1 synaptic transmission in an AD mouse model [ 152 ].…”
Section: Stem Cell-derived Exosomes As a Therapeutic Approach Formentioning
confidence: 56%