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

被引:124
|
作者
Castiglione, Fabio [1 ]
Hedlund, Petter [1 ,2 ]
Van der Aa, Frank [3 ]
Bivalacqua, Trinity J. [4 ]
Rigatti, Patrizio [1 ]
Van Poppel, Hein [3 ]
Montorsi, Francesco [1 ]
De Ridder, Dirk [3 ]
Albersen, Maarten [1 ,3 ]
机构
[1] Univ Vita Salute San Raffaele, Urol Res Inst, Dept Urol, I-20132 Milan, Italy
[2] Linkoping Univ, Dept Clin Pharmacol, Linkoping, Sweden
[3] Katholieke Univ Leuven, Lab Expt Urol Gene & Stem Cells Applicat, Dept Dev & Regenerat, Louvain, Belgium
[4] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Dept Urol, Baltimore, MD 21205 USA
关键词
Antifibrotic; Collagen III; Elastin; Immunohistochemistry; Mesenchymal stromal cells; Polymerase chain reaction; Stem cells; Tunica albuginea; Transforming growth factor beta; Western blot; TUNICA ALBUGINEA; STROMAL CELLS; FIBROBLASTS; MODULATION; RECOVERY; INCREASE; THERAPY;
D O I
10.1016/j.eururo.2012.09.034
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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-mu g transforming growth factor (TGF)-beta 1 in a 50-mu l 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-beta 1 injection with intralesional treatment of vehicle, and the PD plus ADSC group received 1 million human-labeled ADSCs in the 50-mu l 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. (C) 2012 European Association of Urology. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:551 / 560
页数:10
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