Transplantation of Recombinant Vascular Endothelial Growth Factor (VEGF)189-Neural Stem Cells Downregulates Transient Receptor Potential Vanilloid 1 (TRPV1) and Improves Motor Outcome in Spinal Cord Injury
Yun Zeng, Heng Han, Bing Tang, Jie Chen, Dan Mao, Min Xiong
Department of Orthopedics, Dongfeng Hospital Affiliated to Hubei University of Medicine, Shiyan, Hubei, China (mainland)
Med Sci Monit 2018; 24: ANS1089-1096
Spinal cord injury (SCI) causes a rapid loss of motor neurons, leading to weakness and paralysis. Transplantation of neural stem cells is known to restore the neuronal activity but is inefficient due to limited regenerative capability and low rate of survival. There has been an emphasis on the use of growth factors along with neural stem cells (NSCs) to enhance the neuronal recovery. Transplantation of recombinant NSCs with vascular endothelial growth factor (VEGF) might promote neuronal repair. This effect might be attributed to the reduced transient receptor potential vanilloid 1 (TRPV1) expression following transplantation.
MATERIAL AND METHODS: NSCs were cultured from the embryos of Sprague-Dawley rats (E12.5). Four group of rats (n=10, each) were subjected to SCI and allowed to recover for 1 week. Recombinant VEGF-NSCs, normal NSCs and PBS were intrathecally administered to the rats. VEGF and TRPV-1 expression at mRNA and protein level was evaluated. ELISA was performed to determine the release of neurotrophic factors after the transplantation. Motor neurons and axons were counted and the motor behavioral outcome was assessed using the rota-rod test.
RESULTS: VEGF-NSC transgene transplantation resulted in an enhanced neuronal repair and motor behavioral outcome compared to the normal NSCs transplanted group. VEGF-NSCs increased the release of neurotrophic factors and reduced the expression of TRPV1.
CONCLUSIONS: Recombinant VEGF-NSCs transplantation following SCI is more efficacious compared to normal NSC transplantation. This might also be related to a reduced pain in the process of recovery due to reduced TRPV1 expression.
Keywords: neural stem cells, Spinal Cord Injuries, TRPV Cation Channels, Vascular Endothelial Growth Factor A