Rebuilding the brain: A narrative review of glial transplantation in neurological diseases

Glial cells play essential roles in maintaining homeostasis within the central nervous system and their dysfunction is increasingly recognized as a contributing factor in neurodegenerative disease. Consequently, strategies aimed at replacing dysfunctional glia or enhancing their beneficial functions have emerged as promising therapeutic approaches. Recent research on glial transplantation has shown encouraging results in multiple models of neurodegenerative disease, particularly highlighting the neuroprotective potential of glial transplants. This review summarizes current advances in transplantation of glial cells, focusing on strategies to restore glial cell function or amplify their supportive roles in the diseased brain. We searched PubMed for peer-reviewed studies published between January 2015 and April 2025 on glial transplantation in neurological diseases. Relevant articles were selected and synthesized narratively based on glial cell type and proposed therapeutic mechanism. The results showed that astrocyte precursor cells derived from human induced pluripotent stem cells can effectively repair damaged tissue in stroke and spinal cord injury models, leading to improved motor and cognitive functions. Additionally, gene-edited or hypoxic pretreated neural progenitor cells and oligodendrocyte progenitor cells have shown promise in promoting myelin regeneration and reducing lesion volume in various diseases. Transplantation of CRISPR-corrected microglia has been successful in preventing calcification, demyelination, and neuroinflammation in white matter dystrophy mice. Hematopoietic stem cell-derived “microglia-like cells” have demonstrated the ability to clear amyloid-β deposits and restore synaptic plasticity in Alzheimer’s disease models. Challenges include cellular heterogeneity, lack of standardized preparation protocols, toxic lesion environments hindering cellular integration, and unclear long-term safety concerns. The article suggests integrating single-cell sequencing, three-dimensional organoid technology, and biomaterial delivery systems to establish a “precision repair” platform for personalized, scalable, and clinically applicable glial cell therapy. By optimizing glial cell sources, enhancing resilience through gene editing, and combining cell-free secretome, a closed-loop intervention of “protection-repair-regeneration” for neurovascular units can be achieved in both acute and chronic stages. This lays the translational foundation for disease-modifying therapies for neurodegenerative diseases.