RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease

Background Exosomes are lipid-bilayer enclosed nano-sized vesicles that transfer functional cellular proteins, mRNA and miRNAs. Mesenchymal stem cells (MSCs) derived exosomes have been demonstrated to prevent memory deficits in the animal model of Alzheimer’s disease (AD). However, the intravenously...

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Vydané v:Immunity & ageing Ročník 16; číslo 1; s. 10 - 12
Hlavní autori: Cui, Guo-hong, Guo, Hai-dong, Li, Han, Zhai, Yu, Gong, Zhang-bin, Wu, Jing, Liu, Jian-sheng, Dong, You-rong, Hou, Shuang-xing, Liu, Jian-ren
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London BioMed Central 13.05.2019
BioMed Central Ltd
Springer Nature B.V
BMC
Predmet:
Advertising executives
Aging
Alzheimer's disease
Amyloid precursor protein
Animal cognition
Animal models
Antibodies
Astrocytes
Biomedical and Life Sciences
Biomedical materials
Biomedicine
Bone marrow
Brain
Central nervous system
Chemokines
Clinical Nutrition
Cognitive ability
Cytokines
Dementia
Diagnosis
Exosomes
Genetic engineering
Geriatrics/Gerontology
Health care reform
Hippocampus
Immunology
Inflammation
Inflammatory cytokine
Interleukin 10
Interleukin 13
Interleukin 4
Interleukin 6
Ischemia
Laboratory animals
Memory
Mesenchymal stem cells
Mesenchyme
Messenger RNA
MicroRNA
mRNA
Novels
Peptides
Presenilin 1
Proteins
Public Health
Quantum dots
Rabies
Risk factors
RNA
Rodents
Stem cell transplantation
Stem cells
Target marketing
Targeting
Transgenic animals
Transgenic mice
Tumor necrosis factor-α
United States > US
Alzheimer’s disease
Targeting
Inflammatory cytokine
Exosomes
Mesenchymal stem cells
ISSN:1742-4933, 1742-4933
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Shrnutí:Background Exosomes are lipid-bilayer enclosed nano-sized vesicles that transfer functional cellular proteins, mRNA and miRNAs. Mesenchymal stem cells (MSCs) derived exosomes have been demonstrated to prevent memory deficits in the animal model of Alzheimer’s disease (AD). However, the intravenously injected exosomes could be abundantly tracked in other organs except for the targeted regions in the brain. Here, we proposed the use of central nervous system-specific rabies viral glycoprotein (RVG) peptide to target intravenously-infused exosomes derived from MSCs (MSC-Exo) to the brain of transgenic APP/PS1 mice. MSC-Exo were conjugated with RVG through a DOPE-NHS linker. Results RVG-tagged MSC-Exo exhibited improved targeting to the cortex and hippocampus after being administered intravenously. Compared with the group administered MSC-Exo, in the group administered RVG-conjugated MSC-Exo (MSC-RVG-Exo) plaque deposition and Aβ levels were sharply decreased and activation of astrocytes was obviously reduced. The brain targeted exosomes derived from MSCs was better than unmodified exosomes to improve cognitive function in APP/PS1 mice according to Morris water maze test. Additionally, although MSC-Exo injected intravenously reduced the expression of pro-inflammatory mediators TNF-α, IL-β, and IL-6, but the changes of anti-inflammatory factors IL-10 and IL-13 were not obvious. However, administration of MSC-RVG-Exo significantly reduced the levels of TNF-α, IL-β, and IL-6 while significantly raised the levels of IL-10, IL-4 and IL-13. Conclusions Taken together, our results demonstrated a novel method for increasing delivery of exosomes for treatment of AD. By targeting exosomes to the cortex and hippocampus of AD mouse, there was a significant improvement in learning and memory capabilities with reduced plaque deposition and Aβ levels, and normalized levels of inflammatory cytokines.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1742-4933
1742-4933
DOI:10.1186/s12979-019-0150-2