Neural Stem Cell Therapies for Central Nervous System Regeneration: Advances, Challenges, and Integrative Technologies

Abstract Neural stem cells (NSCs) are promising candidates for central nervous system (CNS) regeneration because they self-renew and differentiate into neural lineages. Advances in genome engineering, extracellular vesicles (EVs), biomaterials, organoids, single-cell technologies, and precision medicine have expanded approaches for characterizing, engineering, delivering, and evaluating NSC-based therapies for neurological disorders. CRISPR/Cas9 and related platforms may enable more precise modification of NSC function, while NSC-derived EVs offer potential cell-free strategies. Engineered hydrogels and three-dimensional scaffolds may improve cell survival, engraftment, migration, and integration. Organoids and single-cell omics provide increasingly detailed models of cellular heterogeneity and lineage specification. However, clinical translation remains limited by immune compatibility, tumorigenic risk, manufacturing standardization, graft survival and integration, and regulatory requirements. Rigorous preclinical validation, standardized manufacturing, appropriately designed clinical trials, long-term safety monitoring, and harmonized regulatory frameworks are required before routine clinical application.