title: Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats.
abstract: 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.
authors.affiliation: Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium; Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Castiglione
authors.affiliation: Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
authors.forename: Karel
authors.initials: K
authors.lastname: Dewulf
authors.affiliation: Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium; Department of Urology, Airlangga University/Dr. Soetomo General Hospital, Surabaya, Indonesia.
authors.forename: Lukman
authors.initials: L
authors.lastname: Hakim
authors.affiliation: Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Weyne
authors.affiliation: Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Russo
authors.affiliation: Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Boeri
authors.affiliation: The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.affiliation: Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ridder
authors.affiliation: Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
authors.affiliation: Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium. Electronic address: maarten.albersen@uzleuven.be.
authors.forename: Maarten
authors.initials: M
authors.lastname: Albersen
authors.affiliation: Department of Clinical and Experimental Pharmacology, Lund University, Sweden; Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015153:Blotting, Western; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004549:Elastin / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033581:Stem Cell Transplantation; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014521:Urethra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D014525:Urethral Stricture / Q000517:prevention & control*; D014554:Urination; D014563:Urodynamics
chemical_list: D053773:Transforming Growth Factor beta1; D003094:Collagen; D004549:Elastin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat
keywords: Animal model; Stem cell; Therapy; Urethral stricture