RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease
Abstract 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 intr...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2019-05-01
|
Series: | Immunity & Ageing |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12979-019-0150-2 |
id |
doaj-e838fb007619479b98ddcac911b6d293 |
---|---|
record_format |
Article |
spelling |
doaj-e838fb007619479b98ddcac911b6d2932020-11-25T03:01:08ZengBMCImmunity & Ageing1742-49332019-05-0116111210.1186/s12979-019-0150-2RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s diseaseGuo-hong Cui0Hai-dong Guo1Han Li2Yu Zhai3Zhang-bin Gong4Jing Wu5Jian-sheng Liu6You-rong Dong7Shuang-xing Hou8Jian-ren Liu9Department of Neurology, Shanghai No. 9 People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Neurology, Shanghai No. 9 People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Biochemistry, School of Basic Medicine, Shanghai University of Traditional Chinese MedicineDepartment of Neurology, Shanghai No. 9 People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology, Shanghai No. 9 People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology, Shanghai No. 9 People’s Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical CenterDepartment of Neurology, Shanghai No. 9 People’s Hospital, Shanghai Jiaotong University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12979-019-0150-2Alzheimer’s diseaseExosomesTargetingMesenchymal stem cellsInflammatory cytokine |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Guo-hong Cui Hai-dong Guo Han Li Yu Zhai Zhang-bin Gong Jing Wu Jian-sheng Liu You-rong Dong Shuang-xing Hou Jian-ren Liu |
spellingShingle |
Guo-hong Cui Hai-dong Guo Han Li Yu Zhai Zhang-bin Gong Jing Wu Jian-sheng Liu You-rong Dong Shuang-xing Hou Jian-ren Liu RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease Immunity & Ageing Alzheimer’s disease Exosomes Targeting Mesenchymal stem cells Inflammatory cytokine |
author_facet |
Guo-hong Cui Hai-dong Guo Han Li Yu Zhai Zhang-bin Gong Jing Wu Jian-sheng Liu You-rong Dong Shuang-xing Hou Jian-ren Liu |
author_sort |
Guo-hong Cui |
title |
RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease |
title_short |
RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease |
title_full |
RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease |
title_fullStr |
RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease |
title_full_unstemmed |
RVG-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of Alzheimer’s disease |
title_sort |
rvg-modified exosomes derived from mesenchymal stem cells rescue memory deficits by regulating inflammatory responses in a mouse model of alzheimer’s disease |
publisher |
BMC |
series |
Immunity & Ageing |
issn |
1742-4933 |
publishDate |
2019-05-01 |
description |
Abstract 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. |
topic |
Alzheimer’s disease Exosomes Targeting Mesenchymal stem cells Inflammatory cytokine |
url |
http://link.springer.com/article/10.1186/s12979-019-0150-2 |
work_keys_str_mv |
AT guohongcui rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT haidongguo rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT hanli rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT yuzhai rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT zhangbingong rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT jingwu rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT jianshengliu rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT yourongdong rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT shuangxinghou rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease AT jianrenliu rvgmodifiedexosomesderivedfrommesenchymalstemcellsrescuememorydeficitsbyregulatinginflammatoryresponsesinamousemodelofalzheimersdisease |
_version_ |
1724694850745401344 |