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

• DOI: 10.1186/s12979-019-0150-2
• Publication Date: 2019-05-13T21:58:56Z
• Authors: 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
• Keywords: Exosome

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, intravenously injected could be abundantly tracked other organs except for targeted regions brain. Here, we proposed use central nervous system-specific rabies viral glycoprotein (RVG) peptide target intravenously-infused from MSCs (MSC-Exo) brain transgenic APP/PS1 mice. MSC-Exo were conjugated with RVG through a DOPE-NHS linker.RVG-tagged exhibited improved targeting cortex hippocampus after being administered intravenously. Compared group MSC-Exo, RVG-conjugated (MSC-RVG-Exo) plaque deposition Aβ levels sharply decreased activation astrocytes was obviously reduced. The better than unmodified improve cognitive function mice according Morris water maze test. Additionally, although reduced expression pro-inflammatory mediators TNF-α, IL-β, IL-6, but changes anti-inflammatory factors IL-10 IL-13 not obvious. administration MSC-RVG-Exo significantly IL-6 while raised IL-10, IL-4 IL-13.Taken together, our results novel method increasing delivery treatment AD. By AD mouse, there significant improvement learning capabilities levels, normalized inflammatory cytokines.