Utilizing Neural Stem Cell-Derived Exosomes for the Treatment of Alzheimer's Disease

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Alzheimer's disease (AD) is a progressive neurodegenerative disease and a major cause of dementia. However, there are no effective therapeutics available to prevent or attenuate the progression of AD. Exosomes, 50 - 150 nanometers in diameter extracellular vesicles, have been studied as a potential therapeutic in stroke, diabetes and cardiovascular disorders. Due to their ability to cross the blood-brain-barrier, low toxicity and immunogenicity, exosomes are attractive as a potential therapeutic for AD. Here, we studied the exosomes secreted by neural stem cells in the presence of heat-shock stimulus and tested their therapeutic efficacy in a mouse model of AD. Isolation and characterization of exosomes secreted from heat-shock cells showed higher concentration and larger size in comparison to the exosomes isolated from the cells kept at physiological conditions. Furthermore, an AD mouse model injected with the exosomes isolated from heat-shock neural stem cells exhibited better performance in a series of cognitive and motor function behavioral tests. These data indicate that in response to heat-shock, neural stem cells increase exosome yield and alter exosome morphology and cargo content; thereby, exosomes confer the neuroprotection against AD. Future studies are necessary to determine the mechanism underlying these altered exosome characteristics.

First Advisor

Hongmin Wang

Research Area

Basic Biomedical Science

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