Uptake of Mesenchymal Stem Cell-Derived Exosomes in Mouse Brain through Intranasal Delivery

Exosomes are nanoscale extracellular vesicles that widely participate in intercellular communication. An increasing number of studies have reported on the neuroprotective effects of stem cell-derived exosomes in brain diseases through various delivery methods. However, only a few reports are available on the delivery and uptake of stem cell-derived exosomes in the brains of mice of different ages.

PKH-26-labelled mesenchymal stem cell-derived exosomes were collected, and their uptake was investigated in the brains of mice aged 2 weeks, 2 months, and >6 months, 24 hours after intranasal delivery.

No exosomes were distributed in the whole brains of 2-week-old mice after 24 hours of intranasal delivery. However, a small number of exosomes were found in the olfactory bulb, cortex, and hippocampus of 2-month-old mice, with no exosomes observed in the cerebellum. In contrast, a large number of exosomes were ingested in all brain regions, including the olfactory bulb, cortex, hippocampus, and cerebellum, of >6-month-old mice.

Exosomes can enter the brains of adult mice through intranasal administration, but there are differences in the uptake rate among mice of different ages. These findings provide a theoretical basis for the future clinical administration of exosomes for treating brain disorders.