A Preclinical Study of Cell-seeded Tubularized Scaffolds Specially Secreting LL37 for Reconstruction of Long Urethral Defects

Anticancer Res. 2017 Aug;37(8):4295-4301. doi: 10.21873/anticanres.11822.

Abstract

Aim: We constructed a new artificial, long tubular acellular matrix, seeded with autologous progenitor cells transfected with the sequence to produce the antibiotic peptide LL37 and another two common seeding cells, which might be adopted for patients requiring repair of long segment of the urethra.

Materials and methods: Autologous endothelial progenitor cells transfected by lentiviral vectors expressing antibiotic peptide LL37, as well as urothelial and smooth muscle cells from New Zealand white male rabbits, were cultured and seeded onto preconfigured acellular collagen-based tubular matrices (3 cm in length). Artificial conduits were created again in New Zealand white male rabbits and, then, evaluated by immunohistochemistry after 8 weeks.

Results: Cell-seeded tubularized collagen scaffolds were found to be effective in repairing long urethral defects, whereas scaffolds without cells led to poor tissue development and structures.

Conclusion: The artificial tissue engineered tubularized scaffolds combined with genetic methods resulted in vascularized autologous grafts, which may potentially be used for urethroplasty in patients requiring repair of a long segment of the urethra.

Keywords: LL37; Urethral defect; acellular bladder matrix; endothelial progenitor cells; tissue engineering.

MeSH terms

  • Animals
  • Antimicrobial Cationic Peptides
  • Autografts
  • Cathelicidins / biosynthesis*
  • Cathelicidins / genetics
  • Collagen / chemistry
  • Extracellular Matrix / genetics
  • Extracellular Matrix / metabolism
  • Genetic Vectors
  • Lentivirus / genetics
  • Male
  • Myocytes, Smooth Muscle / metabolism
  • Plastic Surgery Procedures*
  • Rabbits
  • Stem Cells / metabolism
  • Tissue Engineering*
  • Tissue Scaffolds
  • Transfection
  • Urethra / pathology
  • Urethra / surgery*
  • Urothelium / growth & development
  • Urothelium / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • Collagen