title: Intratunical injection of human adipose tissue-derived stem cells prevents fibrosis and is associated with improved erectile function in a rat model of Peyronie's disease.
abstract: BACKGROUND
  Peyronie's disease (PD) is a connective tissue disorder of the tunica albuginea (TA). Currently, no gold standard has been developed for the treatment of the disease in its active phase.
  
  
  OBJECTIVE
  To test the effects of a local injection of adipose tissue-derived stem cells (ADSCs) in the active phase of a rat model of PD on the subsequent development of fibrosis and elastosis of the TA and underlying erectile tissue.
  
  
  METHODS
  A total of 27 male 12-wk-old Sprague-Dawley rats were divided in three equal groups and underwent injection of vehicle (sham), 0.5-μg [corrected] transforming growth factor (TGF)-β1 in a 50-μl vehicle in either a PD or a PD plus ADSC group in the dorsal aspect of the TA.
  
  
  METHODS
  The sham and PD groups were treated 1 d after TGF-β1 injection with intralesional treatment of vehicle, and the PD plus ADSC group received 1 million human-labeled ADSCs in the 50-μl vehicle. Five weeks after treatment, six rats per group underwent erectile function measurement. Following euthanasia, penises were harvested for histology and Western blot.
  
  
  METHODS
  The ratio of intracavernous pressure to mean arterial pressure (ICP/MAP) upon cavernous nerve stimulation, elastin, and collagen III protein expression and histomorphometric analysis of the penis. Statistical analysis was performed by analysis of variance followed by the Tukey-Kramer test for post hoc comparisons or the Mann-Whitney test when applicable.
  
  
  CONCLUSIONS
  Erectile function significantly improved after ADSC treatment (ICP/MAP 0.37 in PD vs 0.59 in PD plus ADSC at 5-V stimulation; p=0.03). PD animals developed areas of fibrosis and elastosis with a significant upregulation of collagen III and elastin protein expression. These fibrotic changes were prevented by ADSC treatment.
  
  
  CONCLUSIONS
  This study is the first to test stem cell therapy in an animal model of PD. Injection of ADSCs into the TA during the active phase of PD prevents the formation of fibrosis and elastosis in the TA and corpus cavernosum.
authors.affiliation: Urological Research Institute, Department of Urology, University Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Castiglione
authors.forename: Petter
authors.initials: P
authors.lastname: Hedlund
authors.forename: Frank
authors.initials: F
authors.lastname: Van der Aa
authors.forename: Trinity J
authors.initials: TJ
authors.lastname: Bivalacqua
authors.forename: Patrizio
authors.initials: P
authors.lastname: Rigatti
authors.forename: Hein
authors.initials: H
authors.lastname: Van Poppel
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Dirk
authors.initials: D
authors.lastname: De Ridder
authors.forename: Maarten
authors.initials: M
authors.lastname: Albersen
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D004548:Elasticity; D004549:Elastin / Q000378:metabolism; D007172:Erectile Dysfunction / Q000473:pathology / Q000628:therapy*; D005355:Fibrosis / Q000517:prevention & control; D006801:Humans; D015552:Injections, Intralesional; D008297:Male; D010410:Penile Erection / Q000502:physiology; D010411:Penile Induration / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation / Q000379:methods*; D014183:Transplantation, Heterologous; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D024061:Collagen Type III; D004549:Elastin