Neural Stem Cell-Derived Extracellular Vesicles: The Next Frontier in Neurological and Neurodegenerative Diseases

The present manuscript provides a comprehensive overview of neural stem cell (NSC)-derived extracellular vesicles (NSC-EVs( as a cell-free approach to treating central nervous system (CNS) disorders. The study noted that NSCs are regenerative and neuroprotective, but direct transplantation is limited by short survival, immunological rejection, and tumorigenic risk. However, NSC-EVs-nano-sized vesicles loaded with proteins, lipids, and RNAs-can replicate many of their parent cells' benefits without safety or ethical issues. NSC-EVs are the source of numerous biologically active molecular cargoes. Encompassing (BDNF, GDNF, VEGF), signaling lipids, and microRNAs (miR-124, miR-21, miR-146a, miR-219) that are essential in modulating and regulating key processes involved in the induction of neurogenesis, promoting angiogenesis, reducing inflammatory milieu, and improving neuronal survival. In preclinical models of Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), ischemic stroke, spinal cord injury (SCI), and traumatic brain injury (TBI), these vesicles reduce oxidative stress, suppress apoptosis, modulate microglia activation, enhance synaptic plasticity, and promote remyelination. Numerous translational obstacles remain, including heterogeneous EV isolation techniques, limited scalability of clinical-grade manufacturing, and inconsistent elucidation of long-term safety and biodistribution. This review discusses the therapeutic potential of NSC-EVs for neurological and neurodegenerative diseases. Additionally, leveraging the powerful, precise analytical capabilities of Artificial Intelligence (AI) with recent multi-omics data from NSC-EVs will improve the characterization and predictability of therapeutic efficacy. Combining the therapeutic potential of stem cells with the non-invasive, practical, and safe cell-free biologic is expected to transform regenerative neuroscience. A promising aim that requires establishing a multidisciplinary approach among neuroscientists, bioengineers, and clinicians to standardize the isolation process, validate the underlying mechanistic information, and test their therapeutic potential at the clinical level. The present review concludes that NSC-EVs are a promising research topic in regenerative neurotherapy, offering a potential therapeutic strategy for incurable neurological and neurodegenerative diseases.