Exosome-based Therapy Eases Disease in MS Mouse Model
Treatment led to fewer inflammatory proteins, inflammatory immune cells
A new therapy that delivers an anti-inflammatory compound to nervous system immune cells via cellular “shipping containers” called exosomes showed promise in a mouse model of multiple sclerosis (MS), a study reports.
The study, “Resveratrol-loaded macrophage exosomes alleviate multiple sclerosis through targeting microglia,” was published in the Journal of Controlled Release.
Exosomes are small packets of cellular cargo, like proteins and RNA, that are wrapped in a membrane. Many cells release exosomes to communicate with each other and coordinate complex biological processes.
Researchers in China developed a method to track the movement of exosomes during laboratory experiments. The process involved modifying sugar molecules, called sialic acid, so they could be tracked with a fluorescent dye.
Once the system was developed, the researchers conducted proof-of-principle tests using exosomes derived from three types of immune cells: macrophages, dendritic cells, or T-cells.
Results showed this could help track the uptake of exosomes in cell models and their movement through mice. During these experiments, the researchers noticed that macrophage-derived exosomes — but not exosomes from the other immune cells — tended to accumulate in the brain and spinal cord.
Specifically, exosomes from macrophages were preferentially taken up by microglia, which are immune cells in the nervous system. Activated microglia are thought to participate in the autoimmune inflammatory attack that drives nervous system damage in MS.
“Inspired by this discovery, we developed [an exosome-based therapy] for multiple sclerosis (MS) treatment,” said the researchers who reasoned that they could package a medication in the macrophage-derived exosomes, allowing it to be directed to microglia. “Our results suggest that [macrophage-derived exosomes] may be an excellent targeted drug delivery system.”
The researchers packaged exosomes with an anti-inflammatory compound called resveratrol (RSV). These RSV-loaded exosomes were then tested in mice with experimental autoimmune encephalitis (EAE), a common model of MS. The exosomes were administered into the mice’s noses at the onset of symptoms.
Compared to untreated EAE mice, those given the RSV-loaded exosomes had a significantly higher body weight and lower clinical score — suggesting less severe disease.
The treatment also led to lower levels of several inflammatory proteins and an examination of the mice’s tissue showed fewer inflammatory immune cells in the central nervous system of the treated mice. Microglial activation was also markedly reduced in mice treated with the RSV-loaded exosomes.
“Engineered [exosomes] loaded with RSV had obvious therapeutic effects and suppressed EAE disease development,” the researchers wrote.
The mice given exosomes showed “no obvious toxicity” in the heart, liver, lungs or kidneys, though the researchers noted they did have abnormal inflammation and cellular changes in their nose tissue.
The researchers concluded that the RSV-loaded exosome treatment “appears to be a promising therapeutic candidate” for MS and their study supports utilizing exosomes to deliver medicines to target cells.
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