elastin and Urethral-Stricture

To present the pathologic analysis of female urethral strictures obtained during reconstructive urethroplasty.. Nine separate female urethral tissue specimens were obtained during dorsal vaginal graft urethroplasty by a single surgeon (S.P.P.). Samples were serially sectioned and fixed in 10% formalin 6 to 12 hours before routine processing in paraffin blocks. Serial 5-µm sections were subjected to H&E, Masson trichrome, and elastin staining. End point analysis included evaluation for epithelial hyperplasia and cell type, mucosal edema, degree of fibroblast/inflammatory cell infiltrate, and elastin fiber density and distribution.. Nine specimens were examined. Six specimens had epithelial linings of stratified squamous epithelium overlying fibrosis (67%), 1 had mixed squamous and urothelial epithelium, and 2 had only urothelial epithelium. Two specimens (29%) showed acute injury with prominent squamous papillary hyperplasia, focal erosion, and patchy mucosal hemorrhage. Areas of urethral stricture were variably thickened, with increased, densely packed collagen fibers and associated mucosal lymphocytic inflammation ranging from mild and patchy to focally dense with lymphoid aggregates. The highest elastin fiber density appeared to be associated with vessels and overlying muscle bundles in the submucosa.. Further elucidation of histopathologic characteristics may illuminate more appropriate therapeutic pathways for female urethral stricture disease management.

Topics: Carcinoma, Squamous Cell; Elastin; Female; Humans; Hyperplasia; Male; Mouth Mucosa; Treatment Outcome; Urethral Stricture; Urothelium

A medical treatment for urethral stricture (US) is not yet available.. To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US.. Male rats were divided into three groups: sham, US, and hADSC (n=12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-β1 in the urethral wall.. One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses.. Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot.. US rats exhibited 49-51% shorter micturition intervals, 35-51% smaller micturition volumes and bladder capacity, 33-62% higher threshold pressures and flow pressures, and 35-37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p<0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34-55% smaller contractions than detrusor from sham rats (p<0.05). Corresponding values were 11-35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p<0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p<0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study.. Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US.. Stem cell therapy is effective for preventing urethral stricture in an experimental setting.

Topics: Adipose Tissue; Animals; Blotting, Western; Collagen; Disease Models, Animal; Elastin; Fibrosis; Humans; Male; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Stem Cell Transplantation; Transforming Growth Factor beta1; Urethra; Urethral Stricture; Urination; Urodynamics

Topics: Adolescent; Adult; Age Factors; Aged; Autopsy; Child; Child, Preschool; Collagen; Elasticity; Elastin; Estrogens; Female; Humans; Hydroxyproline; Infant; Infant, Newborn; Male; Middle Aged; Pregnancy; Sex Factors; Staining and Labeling; Urethra; Urethral Diseases; Urethral Stricture; Urination Disorders