Transplantation of vascular endothelial growth factor-transfected neural stem cells into the rat brain provides neuroprotection after transient focal cerebral ischemia

Objective: Vascular endothelial growth factor (VEGF) stimulation and neural stem cell (NSC) transplantation have been implicated in the treatment of cerebral ischemia because of their crucial roles in neuroprotection, neurogenesis, and angiogenesis: However, effective delivery of VEGF or NSCs remains difficult. This study attempted to explore whether VEGF(121) complementary deoxyribonucleic acid could be transferred into the NSCs and, furthermore, whether transplanting these VEGF(121)-transfected NSCs into the rat brain provides sufficient neuroprotection after transient focal cerebral ischemia. Methods: The VEGF(121) gene was transfected to the NSCs isolated from E14 fetal rat hippocampus. In vitro studies revealed that VEGF messenger ribonucleic acid could be consistently expressed in NSCs from 1 day to up to 2 weeks. Results: After transplantation of VEGF(121)-transfected NSCs into the perifocal area of the ischemic rat brain, we found that these cells could survive and migrate in the ischemic region for 12 weeks. Furthermore, we observed a significant improvement of the Neurological Severity Scale score in the rats transplanted with VEGF(121)-transfected NSCs in comparison to the phosphate-buffered saline-injected or the sham-operated rats (P<0.05). Transplantation of nontransfected NSCs into ischemic rat brain improved the Neurological Severity Scale score as well. Of note, the improvement in, the Neurological Severity Scale score occurred earlier in the VEGF(121)-transfected NSC rats than in the nontransfected NSC rats (range, 2-12 wk versus 8-12 wk), suggesting a potent neuroprotection mediated by additional VEGF(121) transfection. Conclusion: We conclude that transplantation of VEGF(121)-transfected NSCs improved ischemic neurological deficiency. This finding provides a novel approach for the treatment of cerebral ischemia.