Neural stem cell derived extracellular vesicles – attributes and prospects for treating neurodegenerative disorders

Neural stem cell (NSC) grafting in conditions such as aging, brain injury, and neurodegenerative diseases promotes regeneration, plasticity and functional recovery. Recent studies have revealed that administration of NSC-derived extracellular vesicles (NSC-EVs) via non-invasive approaches can also afford therapeutic benefits. Here, researchers from Texas A&M University Health Science Center review the properties and therapeutic promise of EVs secreted by NSCs. NSC-EVs enriched with specific miRNAs mediate multiple functions in physiological and pathological conditions, which include modulation of the proximate microenvironment, facilitating the entry of viruses into cells, functioning as independent metabolic units, operating as a microglial morphogen and influencing the diverse aspects of brain function in adulthood including the process of aging. Due to their anti-inflammatory, neurogenic and neurotrophic effects, NSC-EVs are also useful for treating multiple neurodegenerative diseases. Although only a few studies have demonstrated the efficacy of NSC-EVs to treat brain impairments, the promise is enormous. Moving forward, the use of well-characterized NSC-EVs generated in specific culture conditions and NSC-EVs that are engineered to carry the desired miRNAs, mRNAs and proteins have great promise for treating brain injury and neurogenerative diseases. Notably, the possibility of targeting NSC-EVs to specific neuronal types or brain regions would enable managing of diverse neurodegenerative conditions with minimal side effects.

A schematic depicting the various known functions of
neural stem cell-derived extracellular vesicles (NSC-EVs)

exosomes

NSC-EVs have so far been found to involved in multiple activities. These include mediating the viral entry into cells via a receptor-independent fashion, regulating specific downstream signaling pathways in target cells, and functioning as independent metabolic units via L-asparaginase activity. Moreover, NSC-EVs have been shown to promote neuroprotection in the mouse and porcine models of stroke facilitating recovery after necrotic enterocolitis and acting as a microglial morphogen to modulate microglia activity during brain development. Additionally, NSC-EVs have been shown to control the process of aging through specific EVs released from the hypothalamus.

Vogel A, Upadhya R, Shetty AK. (2018) Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders. EBioMedicine [Epub ahead of print]. [article]

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