title: Adipose tissue-derived stem cell therapy for prevention and treatment of erectile dysfunction in a rat model of Peyronie's disease.
abstract: Peyronie's disease (PD) is a localized connective tissue disorder that involves the tunica albuginea (TA) of the penis. While surgical correction remains the gold standard, the search for an effective and less invasive therapy continues. The objective of this study was to evaluate the effects of intratunical injection of adipose tissue-derived stem cells (ADSCs) for the prevention and treatment of erectile dysfunction in a rat model of PD. Twenty-four male Sprague-Dawley rats (300-350 g) were randomly divided into four groups: sham, PD, PD + ADSC (prevention) and PD + ADSC (treatment). All rats underwent penile injections into the TA with 50 μL vehicle (sham) or 0.5 μg transforming growth factor (TGF)-β1 (remaining groups). The ADSC groups received intratunical injections with 0.5 million rat-labelled ADSCs on day 0 (prevention) or day 30 (treatment). Forty-five days following TGF-β1 injection, rats underwent cavernous nerve stimulation (CNS) with total intracavernous-to-mean arterial pressure ratio (ICP/MAP) and total ICP recorded to measure response to therapy. Tissues were evaluated histologically and for mRNA expression of tissue inhibitors of metalloproteinases (TIMPs), matrix metalloproteinases (MMPs) and zymographic activity of MMPs. Statistical analysis was performed by analysis of variance followed by the Tukey test for post hoc comparisons. In both prevention and treatment groups, intratunical injection of ADSCs resulted in significantly higher ICP/MAP and total ICP in response to CNS compared with the PD group. Local injection of ADSCs prevented and/or reduced Peyronie's-like changes by decreasing the expression of TIMPs, and stimulating expression and activity of MMPs. This study documents the preventive and therapeutic benefits of ADSC on penile fibrosis and erectile function in an animal model of PD.
authors.affiliation: Department of Urology, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Gokce
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Abd Elmageed
authors.forename: G F
authors.initials: GF
authors.lastname: Lasker
authors.forename: M
authors.initials: M
authors.lastname: Bouljihad
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: L W
authors.initials: LW
authors.lastname: Trost
authors.forename: P J
authors.initials: PJ
authors.lastname: Kadowitz
authors.forename: A B
authors.initials: AB
authors.lastname: Abdel-Mageed
authors.forename: S C
authors.initials: SC
authors.lastname: Sikka
authors.forename: W J
authors.initials: WJ
authors.lastname: Hellstrom
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D062186:Arterial Pressure; D002426:Cavernous Sinus / Q000294:innervation; D064987:Cell- and Tissue-Based Therapy; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy*; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics; D010410:Penile Erection; D010411:Penile Induration / Q000628:therapy*; D010413:Penis / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D004561:Transcutaneous Electric Nerve Stimulation; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D053773:Transforming Growth Factor beta1; D020782:Matrix Metalloproteinases
keywords: Peyronie's disease; erectile function; fibrosis; stem cells; tunica albuginea