Transplantation of Vascular Endothelial Growth... : Neurosurgery (original) (raw)

Experimental Studies: CELLULAR BIOLOGY: CELLULAR AND MOLECULAR NEUROSURGERY: CEREBROVASCULAR: NEUROPROTECTION

Transplantation of Vascular Endothelial Growth Factor-transfected Neural Stem Cells into the Rat Brain Provides Neuroprotection after Transient Focal Cerebral Ischemia

Zhu, Wei M.D.; Mao, Ying M.D., Ph.D.; Zhao, Yao M.D., Ph.D.; Zhou, Liang-Fu M.D.; Wang, Yang M.D.; Zhu, Jian-Hong M.D.; Zhu, Yuan M.D., Ph.D.; Yang, Guo-Yuan M.D., Ph.D.

Institution of Neurosurgery, Hua-Shan Hospital, Fudan University, Shanghai, China (W Zhu, Mao, Zhao, Zhou, JH Zhu)

Departments of Anatomy,Histology, and Embryology,Shanghai Medical School,Fudan University, Shanghai, China (Wang)

Institut für Pharmakologie und Toxikologie, Philipps-Unversität, Marburg, Germany (Zhu)

Institution of Neurosurgery, Hua-Shan Hospital, Fudan University, Shanghai, China, and Center for Cerebrovascular Research, Departments of Anesthesia and Neurosurgery, University of California, San Francisco, San Francisco, California (Yang)

Reprint requests: Guo-Yuan Yang, M.D., Ph.D., The Center for Cerebrovascular Research, Departments of Anesthesia and Neurosurgery, University of California, San Francisco, Box 1371, 1001 Potrero Avenue, San Francisco, CA 94110.Email: [email protected]

Received, July 29, 2004.

Accepted, February 16, 2005.

Abstract

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.

CONCLUSION:

We conclude that transplantation of VEGF121-transfected NSCs improved ischemic neurological deficiency. This finding provides a novel approach for the treatment of cerebral ischemia.