Penile urethra replacement with autologous cell-seeded tubularized collagen matrices

Roger E. De Filippo, Benjamin S. Kornitzer, James J. Yoo, Anthony Atala

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Acellular collagen matrices have been used as an onlay material for urethral reconstruction. However, cell-seeded matrices have been recommended for tubularized urethral repairs. In this study we investigated whether long segmental penile urethral replacement using autologous cell-seeded tubularized collagen-based matrix is feasible. Autologous bladder epithelial and smooth muscle cells from nine male rabbits were grown and seeded onto preconfigured tubular matrices constructed from decellularized bladder matrices obtained from lamina propria. The entire anterior penile urethra was resected in 15 rabbits. Urethroplasties were performed with tubularized matrices seeded with cells in nine animals, and with matrices without cells in six. Serial urethrograms were performed at 1, 3 and 6 months. Retrieved urethral tissues were analysed using histo- and immunohistochemistry, western blot analyses and organ bath studies. The urethrograms showed that animals implanted with cell-seeded matrices maintained a wide urethral calibre without strictures. In contrast, the urethras with unseeded scaffolds collapsed and developed strictures. Histologically, a transitional cell layer surrounded by muscle was observed in the cell-seeded constructs. The epithelial and smooth muscle phenotypes were confirmed with AE1/AE3 and α-actin antibodies. Organ bath studies of the neourethras confirmed both physiological contractility and the presence of neurotransmitters. Tubularized collagen matrices seeded with autologous cells can be used successfully for long segmental penile urethra replacement, while implantation of tubularized collagen matrices without cells leads to poor tissue development and stricture formation. The cell-seeded collagen matrices are able to form new tissue, which is histologically similar to native urethra.

Original languageEnglish (US)
Pages (from-to)257-264
Number of pages8
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume9
Issue number3
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

Keywords

  • Autologous cells
  • Cell seeding
  • Collagen matrix
  • Penile urethral replacement
  • Tubularized urethral repair

ASJC Scopus subject areas

  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Biomaterials

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