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

• Published in: European urology 2013-03, Vol.63 (3), p.551-560
• Main Authors: Castiglione, Fabio, Hedlund, Petter, Van der Aa, Frank, Bivalacqua, Trinity J, Rigatti, Patrizio, Van Poppel, Hein, Montorsi, Francesco, De Ridder, Dirk, Albersen, Maarten
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Animals; Antifibrotic; Biological and medical sciences; Biomarkers - metabolism; Collagen III; Collagen Type III - metabolism; Elasticity; Elastin; Elastin - metabolism; Erectile Dysfunction - pathology; Erectile Dysfunction - therapy; Fibrosis - prevention & control; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Injections, Intralesional; Male; Male genital diseases; Medical sciences; Mesenchymal stromal cells; Nephrology. Urinary tract diseases; Non tumoral diseases; Penile Erection - physiology; Penile Induration - pathology; Penile Induration - therapy; Polymerase chain reaction; Rats; Rats, Sprague-Dawley; Stem Cell Transplantation - methods; Stem cells; Transforming growth factor beta; Transplantation, Heterologous; Treatment Outcome; Tunica albuginea; Urology; Western blot
• ISSN: 0302-2838; 1873-7560; 1873-7560
• DOI: 10.1016/j.eururo.2012.09.034

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. Design, setting, and participants A total of 27 male 12-wk-old Sprague-Dawley rats were divided in three equal groups and underwent injection of vehicle (sham), 50-μg 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. Intervention 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. Outcome measurements and statistical analysis 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. Results and limitations 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.