Neural stem cells (NSCs) represent a promising therapeutic strategy for repairing damaged neural circuits in the central nervous system (CNS). The therapeutic promise of NSCs stems from their dual capacity for sustained self-renewal and differentiation into neurons, astrocytes, and oligodendrocytes, which collectively support the regeneration of injured neural tissue and the recovery of neurological function. Beyond direct cell replacement, NSCs exert powerful paracrine effects through the secretion of neurotrophic factors, cytokines, and extracellular vesicles that modulate inflammation, enhance neuronal survival, and promote axonal regeneration. Increasing evidence indicates that NSC-mediated immunomodulation plays a central role in shifting the post-injury microenvironment from a neurotoxic to a regenerative state, primarily through regulation of microglial polarization and suppression of pro-inflammatory signaling pathways.
In addition, NSCs contribute to neural repair by enhancing synaptic plasticity, supporting remyelination, stabilizing the blood–brain barrier, and facilitating angiogenesis. Accumulating preclinical evidence suggests that both NSC transplantation and the therapeutic application of NSC-derived secretomes lead to significant functional improvement in animal models of spinal cord injury, stroke, and traumatic brain injury. However, clinical translation remains limited by challenges such as poor cell survival, immune rejection, tumorigenic risk, and lack of standardized delivery protocols. Emerging strategies, including gene-edited NSCs, biomaterial scaffolds, and exosome-based cell-free therapies, are being developed to overcome these limitations. Overall, NSCs provide a multifaceted regenerative platform with strong potential for future clinical applications in neurological disorders, although further large-scale clinical studies are essential to validate the long-term safety and efficacy of these therapies.