GDNF-Transduced Schwann Cell Grafts Enhance Regeneration of Erectile Nerves

• Published in: European urology Vol. 54; no. 5; pp. 1179 - 1187
• Main Authors: May, Florian, Matiasek, Kaspar, Vroemen, Maurice, Caspers, Christiane, Mrva, Thomas, Arndt, Christian, Schlenker, Boris, Gais, Peter, Brill, Thomas, Buchner, Alexander, Blesch, Armin, Hartung, Rudolf, Stief, Christian, Gansbacher, Bernd, Weidner, Norbert
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.11.2008; Elsevier
• Subjects: Animals; Axons - physiology; Axons - ultrastructure; Biological and medical sciences; Cell Transplantation - methods; Cells, Cultured; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Erectile Dysfunction - metabolism; Erectile Dysfunction - physiopathology; Erectile Dysfunction - surgery; Erection; GDNF; Gene therapy; Glial Cell Line-Derived Neurotrophic Factor - biosynthesis; Immunohistochemistry; Male; Medical sciences; Microscopy, Electron; Nephrology. Urinary tract diseases; Nerve grafts; Nerve Regeneration - physiology; Neurotrophic factor; Penile Erection - physiology; Penis - innervation; Penis - surgery; Rats; Rats, Inbred F344; Recovery of Function - physiology; Schwann cells; Schwann Cells - metabolism; Schwann Cells - transplantation; Schwann Cells - ultrastructure; Urology; Neurotrophic factor; Nerve grafts; GDNF; Gene therapy; Erection; Schwann cells; Nephrology; Neuroglia; Urology; Nerve; Regeneration; Treatment; Schwann cell; Graft; Transduction
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2008.02.003

Abstract Background Schwann cell–seeded guidance tubes have been shown to promote cavernous nerve regeneration, and the local delivery of neurotrophic factors may additionally enhance nerve regenerative capacity. The present study evaluates whether the transplantation of GDNF-overexpressing Schwann cells may enhance regeneration of bilaterally transected erectile nerves in rats. Methods Silicon tubes seeded with either GDNF-overexpressing or GFP-expressing Schwann cells were implanted into the gaps between transected cavernous nerve endings. Six (10 study nerves) or 12 wk (20 study nerves) postoperatively, erectile function was evaluated by relaparotomy, electrical nerve stimulation, and intracavernous pressure recording, followed by ultrastructural evaluation of reconstructed nerves employing bright-field and electron microscopy. Additional animals were either sham-operated (positive control; 20 study nerves) or received bilateral nerve transection without nerve reconstruction (negative control; 20 study nerves). Results The combination of GDNF delivery and Schwann cell application promoted an intact erectile response in 90% (9 of 10) of grafted nerves after 6 wk and in 95% (19 of 20) after 12 wk, versus 50% (5 of 10) and 80% (16 of 20) of GFP-expressing Schwann cell grafts ( p = 0.02). The functional recovery was paralleled by enhanced axonal regeneration in GDNF-overexpressing Schwann cell grafts, as indicated by larger cross-sectional areas and a significantly higher percentage of neural tissue compared with GFP-transduced controls. Conclusions These findings demonstrate that the time required to elicit functional recovery of erectile nerves can be reduced by local delivery of GDNF. In terms of clinical application, this enhanced nerve repair might be critical for timely reinnervation of the corpus cavernosum as a prerequisite for functional recovery in men.