Articles

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

By: Fabio Castiglionea, Petter Hedlunda b lowast , Frank Van der Aac, Trinity J. Bivalacquad, Patrizio Rigattia, Hein Van Poppelc, Francesco Montorsia, Dirk De Ridderc and Maarten Albersena c

Published online: 01 March 2013

Keywords: Antifibrotic, Collagen III, Elastin, Immunohistochemistry, Mesenchymal stromal cells, Polymerase chain reaction, Stem cells, Tunica albuginea, Transforming growth factor beta, Western blot

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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.

Take Home Message

Early injection of adipose tissue–derived stem cells into an induced Peyronie's plaque prevents formation of fibrosis and elastosis in the tunica and dorsal corpus cavernosum, and it preserves erectile function in a rat model of Peyronie's disease.

Keywords: Antifibrotic, Collagen III, Elastin, Immunohistochemistry, Mesenchymal stromal cells, Polymerase chain reaction, Stem cells, Tunica albuginea, Transforming growth factor beta, Western blot.

Footnotes

a Urological Research Institute, Department of Urology, University Vita–Salute San Raffaele, Milan, Italy

b Department of Clinical Pharmacology, Linköping University, Linköping, Sweden

c Laboratory for Experimental Urology, Gene and Stem Cells Applications, Department of Development and Regeneration, University of Leuven, Leuven, Belgium

d The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA

lowast Corresponding author. Urological Research Institute, University Vita–Salute San Raffaele, Via Olgettina, 60, 20132 Milan, Italy. Tel. +39 02 26436269; Fax: +39 02 26435659.