title: Intratunical Injection of Genetically Modified Adipose Tissue-Derived Stem Cells with Human Interferon α-2b for Treatment of Erectile Dysfunction in a Rat Model of Tunica Albugineal Fibrosis.
abstract: BACKGROUND
  Peyronie's disease (PD) has frequently been associated with erectile dysfunction (ED) and may further compromise coitus.
  
  
  OBJECTIVE
  To investigate the efficacy of intratunical injection of genetically modified rat adipose tissue-derived stem cells (ADSCs) expressing human interferon α-2b (ADSCs-IFN) in decreasing fibrosis and restoring erectile function in a rat model of tunica albugineal fibrosis (TAF).
  
  
  METHODS
  A total of 36 Sprague-Dawley rats (12 weeks old; 300-350 g) were randomly divided in six equal groups: (i) sham group (50 μL saline-injected into the tunica albuginea [TA]); (ii) TAF group (transforming growth factor [TGF]-β1 [0.5 μg/50 μL] injected into the TA); (iii) TGF-β1 plus 5 × 10(5) control ADSCs injected same day; (iv) TGF-β1 plus 5 × 10(5) ADSCs-IFN injected same day; (v) TGF-β1 plus 5 × 10(5) control ADSCs injected after 30 days; and (vi) TGF-β1 plus 5 × 10(5) ADSCs-IFN injected after 30 days. Rat allogeneic ADSCs were harvested from inguinal fat tissue.
  
  
  METHODS
  Forty-five days following the TGF-β1 injection, erectile function was assessed, and penile tissues were harvested for further evaluations.
  
  
  RESULTS
  In the same-day injection groups, intratunical injection of ADSCs and ADSC-IFN improved erectile response observed upon stimulation of cavernous nerve compared with TAF group. Intratunical ADSC-IFN injection at day 30 improved erectile responses 3.1, 1.8, and 1.3 fold at voltages of 2.5, 5.0, and 7.0, respectively, when compared with TAF group. Furthermore, at voltages of 2.5 and 5.0, treatment on day 30 with ADSCs-IFN improved erectile responses 1.6- and 1.3-fold over treatment with ADSCs alone. Local injection of ADSCs or ADSCs-IFN reduced Peyronie's-like manifestations, and these effects might be associated with a decrease in the expression of tissue inhibitors of metalloproteinases.
  
  
  CONCLUSIONS
  This study documents that transplantation of genetically modified ADSCs, with or without human IFN α-2b, attenuated Peyronie's-like changes and enhanced erectile function in a rat model of TAF.
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.|Department of Urology, Sakarya University School of Medicine, Sakarya, Turkey.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Gokce
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Zakaria Y
authors.initials: ZY
authors.lastname: Abd Elmageed
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Lasker
authors.affiliation: Tulane National Primate Research Center, New Orleans, LA, USA.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Bouljihad
authors.affiliation: Tulane National Primate Research Center, New Orleans, LA, USA.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Braun
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Hogyoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Asim B
authors.initials: AB
authors.lastname: Abdel-Mageed
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Sikka
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: Wayne J
authors.initials: WJ
authors.lastname: Hellstrom
mesh_terms: D000273:Adipose Tissue / Q000637:transplantation*; D000818:Animals; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000628:therapy*; D005355:Fibrosis / Q000628:therapy; D006801:Humans; D015552:Injections, Intralesional; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D010411:Penile Induration / Q000628:therapy*; D010413:Penis / Q000294:innervation / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D033581:Stem Cell Transplantation
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins
keywords: Erectile Dysfunction; Fibrosis; Gene Therapy; Human Interferon α-2b; Peyronie's Disease; Stem Cells; Tunica Albuginea