Vascular Endothelial Growth Factor Gene Therapy Promotes Nerve Regeneration in a Sciatic Nerve Graft Model in Rats
Authors
T.Holzbach1, R. Miliojcic1, K. Matiasek2, M.A. Konerding3, M. Anton4, A. Feuchtinger5, J. Schlegel6, E. Volkmer1, C. Krug1 and R.E. Giunta1 1Dept. of Hand Surgery, Plastic Surgery, Aesthetic Surgery, Ludwig-Maximilians-Universität, Munich, Germany; 2Institute of Veterinarian Pathology, Ludwig-Maximilians-Universität, Munich, Germany; 3Institute of Anatomy and Cell Biology, Johannes Gutenberg University, Mainz, Germany; 4Institute of Experimental Oncology, Technische Universität München, Ismaninger Straße 22, Munich, Germany; 5Institute of Pathology, Helmholtz Zentrum, Munich, Germany; 6Department of Neuropathology, Technische Universität München, Munich, Germany
Incomplete nerve regeneration after injuries to the peripheral nervous system remains a significant problem in clinical routine and raises the need for supportive strategies. In this study we examined the effect of VEGF-gene therapy on nerve recovery after an auto-graft implantation in a 2 cm sciatic nerve defect model in 18 rats, using an adenoviral vector encoding for VEGF165 (AdCMV.VEGF165) for gene transduction. Functional recovery was assessed weekly by gait analyses of the rats’ hind limbs. Morphometric evaluation including histology, axon counts, motor neuron counts and corrosion casting was carried out 18 weeks post-op. VEGF-treated animals contained a higher proportion of large axons in the distal part of the nerve grafts and the SFI (Sciatic Function Index) showed faster nerve regeneration (p<0.05). There was no change in the vascular architecture of the nerve grafts. These results indicate the positive impact of VEGF gene therapy on nerve recovery in the PNS. VEGF gene therapy led to a significant improvement of the motor-functional parameters and showed accelerated recovery at the histomorphological level. This effect does not seem to be due to better vascularization of the nerve grafts. The use of an adenoviral vector should be be viewed critically.
