Abstract
Background: Stroke is a leading global health concern, with cerebral infarction accounting for 62% of cases. Despite advances in acute-phase treatments, functional impairments such as motor deficits remain prevalent. This study investigates the potential of human induced pluripotent stem cell (iPSC)-derived cerebral cortical neurons for neural regeneration and motor function recovery in a female mouse model of ischemic stroke. Methods: Cerebral infarction was induced using the Rose Bengal photothrombosis method, followed by transplantation of iPSC-derived cortical neurons into the area adjacent to the infarction. Behavioral recovery was assessed using the foot fault and cylinder tests. Histological analysis was performed to evaluate graft integration and neurite extension. Results: Foot fault test demonstrated significant improvements in fine motor function in the transplantation group compared to the vehicle group. However, no recovery was observed in the cylinder test, which assesses gross motor function. Neurite extension from grafted cells was observed along the corticospinal tract, with axonal projections reaching the spinal cord in 68% of transplanted mice. In addition, neurite outgrowth extended to the thalamus, superior colliculus, and vestibular nucleus, suggesting integration into multiple neural circuits. Histological analysis revealed that 16.4% and 47.3% of grafted cells expressed CTIP2 and SATB2, respectively, indicating the presence of both deep- and upper-layer cortical neurons. Conclusions: This study demonstrates that iPSC-derived cortical neurons extend axons along the corticospinal tract and can promote fine motor recovery after stroke. However, further research is needed to validate functional connectivity and long-term safety. These findings offer a promising avenue for developing cell-based therapies for stroke patients.