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 VEGF121 complementary deoxyribonucleic acid could be transferred into the NSCs and, furthermore, whether transplanting these VEGF121-transfected NSCs into the rat brain provides sufficient neuroprotection after transient focal cerebral ischemia.


METHODS
The VEGF121 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 VEGF121-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 VEGF121-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 VEGF121-transfected NSC rats than in the nontransfected NSC rats (range, 2-12 wk versus 8-12 wk), suggesting a potent neuroprotection mediated by additional VEGF121 transfection.


CONCLUSIONS
We conclude that transplantation of VEGF121-transfected NSCs improved ischemic neurological deficiency. This finding provides a novel approach for the treatment of cerebral ischemia.
Zhu
Wei
W
Institution of Neurosurgery, Hua-Shan Hospital, Fudan University, Shanghai, China.
Mao
Ying
Y
Zhao
Yao
Y
Zhou
Liang-Fu
LF
Wang
Yang
Y
Zhu
Jian-Hong
JH
Zhu
Yuan
Y
Yang
Guo-Yuan
GY
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival; D007150:Immunohistochemistry / Q000379:methods; D002546:Ischemic Attack, Transient / Q000628:therapy*; D008297:Male; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000627:therapeutic use*
D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D001973:Bromodeoxyuridine