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

Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.