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May, F.* ; Matiasek, K.* ; Vroemen, M.* ; Caspers, C.* ; Mrva, T.* ; Arndt, C.* ; Schlenker, B.* ; Gais, P. ; Brill, T.* ; Buchner, A.* ; Blesch, A.* ; Hartung, R.* ; Stief, C.* ; Gansbacher, B.* ; Weidner, N.*

GDNF-transduced Schwann cell grafts enhance regeneration of erectile nerves.

Eur. Urol. 54, 1179-1187 (2008)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Erection; Nerve grafts; Schwann cells; GDNF; Neurotrophic factor; Gene therapy
Sprache englisch
Veröffentlichungsjahr 2008
HGF-Berichtsjahr 2008
ISSN (print) / ISBN 0302-2838
e-ISSN 0302-2838
Zeitschrift European Urology
Quellenangaben Band: 54, Heft: 5, Seiten: 1179-1187 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pathology (PATH)
Research Unit Analytical Pathology (AAP)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-500300-001
G-500390-001
DOI 10.1016/j.eururo.2008.02.003
Scopus ID 55649083913
Erfassungsdatum 2008-12-09
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