title: Transplantation of Amniotic Scaffold-Seeded Mesenchymal Stem Cells and/or Endothelial Progenitor Cells From Bone Marrow to Efficiently Repair 3-cm Circumferential Urethral Defect in Model Dogs.
abstract: The treatment options for patients with a urethral defect are limited by the availability of autologous tissues. We hypothesized that transplantation of decellularized human amniotic scaffolds (dHAS) seeded with allogeneic bone marrow mesenchymal cells (BMSCs) and/or endothelial progenitor cells (EPCs) may serve as a promising repair strategy for long segment of circumferential urethral defect. To verify the hypothesis, with urinary catheterization, a 3-cm segment of whole urethra in 25 male mongrel dogs was excised and replaced by dHAS seeded with allogeneic BMSCs and/or EPCs. Postoperative observation and ascending urethrogram found that dHAS+BMSCs+EPCs and dHAS+EPCs groups demonstrated unhindered urination and capacious urethral caliber, which were similar to the normal group, while urethrostenosis was revealed in dHAS+BMSCs, dHAS, and sham-operated groups, with the shortest narrow section in dHAS+BMSCs group and the longest in sham-operated group. Urethral anatomy check and histological analyses showed that new urethral mucosa composed of stratified columnar epithelium completely covered on the inner surface of the graft site in dHAS+BMSCs+EPCs and dHAS+EPCs groups, but the middle epithelium was thin in dHAS+EPCs group, while incompletely covered in dHAS+BMSCs, dHAS, and sham-operated groups, and there were monolayer epithelial cells at the urethrostenosis in dHAS+BMSCs and dHAS groups. In addition, abundant new vessel and blood sinus showed at submucosa in dHAS+BMSCs+EPCs and dHAS+EPCs groups, instead of the scar tissue of collagen deposition and structural distortion at the urethrostenosis in dHAS+BMSCs, dHAS, and sham-operated groups. This study demonstrates that dHAS seeded with BMSCs+EPCs or EPCs can successfully repair a 3-cm circumferential urethral defect in model dogs, but the former works best. This technology may provide some references for human clinical trials on long segment of circumferential urethral defect repair.
authors.affiliation: College of Veterinary Medicine, Northwest A & F University , Yangling, China .
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A & F University , Yangling, China .
authors.forename: Shuxin
authors.initials: S
authors.lastname: Zheng
authors.affiliation: College of Veterinary Medicine, Northwest A & F University , Yangling, China .
authors.forename: Xinke
authors.initials: X
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest A & F University , Yangling, China .
authors.forename: Pengxiu
authors.initials: P
authors.lastname: Dai
authors.affiliation: College of Veterinary Medicine, Northwest A & F University , Yangling, China .
authors.forename: Yongping
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Veterinary Medicine, Northwest A & F University , Yangling, China .
authors.forename: Liangliang
authors.initials: L
authors.lastname: Nan
authors.affiliation: College of Veterinary Medicine, Northwest A & F University , Yangling, China .
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D004285:Dogs; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D014521:Urethra / Q000166:cytology*
keywords: amniotic membrane scaffold; bone marrow mesenchymal stem cells; circumferential urethral defect; dogs; endothelial progenitor cells