Collagen cell carriers seeded with human urothelial cells for urethral reconstructive surgery: first results in a xenograft minipig model
Authors
Stefan Aufderklamm · Martin Vaegler · Alexandra Kelp · Sabine Maurer · Leon Gustafsson · Jens Mundhenk · Silke Busch · Lisa Daum · Arnulf Stenzl · Bastian Amend · Karl‑Dietrich Sievert
Institution
Eberhard Karls University Tuebingen
Country
Germany
Year
2017
Journal
World Journal of Urology
Abstract
Purpose Urethral strictures are a common disease of the
lower urinary tract in men. At present, the use of buccal
mucosa is the method of choice for long or recurrent strictures.
However, autologous tissue-engineered grafts are
still under investigation for reconstructive urological surgery.
The aim of this pilot study was to evaluate the use
of human urothelial cells (HUC) seeded on bovine collagen
type I-based cell carriers (CCC) in an animal model and to
evaluate short-term outcome of the surgical procedure.
Methods Four male Göttingen minipigs were used with
immunosuppression (cyclosporine A) for this pilot xenograft
study. HUC obtained from human benign ureteral tissue
were stained by PKH26 and seeded on a collagen cell
carrier (CCC). Seven weeks after urethral stricture induction
and protective vesicostomy, cell-seeded CCC was
implanted in the urethra with HUC luminal and antiluminal,
respectively. After two weeks animals were euthanized,
urethrography and histological assessment were performed.
Results Surgery was technically feasible in all minipigs.
Stricture was radiologically established 7 weeks after
induction. CCC was visible after two weeks and showed
good integration without signs of inflammation or rejection.
In the final urethrography, no remaining stricture could be
detected. Near porcine urothelium, PKH26-positive areas
were found even if partially detached from CCC. Although
diminished, immunofluorescence with pankeratin, CK20,
E-cadherin and ZO-1 showed intact urothelium in several
areas on and nearby CCC.
Conclusion Finally, this study demonstrates that the HUCseeded
CCC used as a xenograft in minipigs is technically
feasible and shows promising results for further studies.