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Intratunical Injection of Human Adipose Tissue-derived Stem Cells Prevents Fibrosis and Is Associated with Improved Erectile Function in a Rat Model of Peyronies Disease
University of Vita Salute San Raffaele, Milan, Italy .
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Pharmacology.
Katholieke University of Leuven, Belgium .
Johns Hopkins Medical Institute, Baltimore, MD, USA.
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2013 (English)In: European Urology, ISSN 0302-2838, E-ISSN 1873-7560, Vol. 63, no 3, 551-560 p.Article in journal (Refereed) Published
Abstract [en]

Background: Peyronies 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. less thanbrgreater than less thanbrgreater thanObjective: 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. less thanbrgreater than less thanbrgreater thanDesign, 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. less thanbrgreater than less thanbrgreater thanIntervention: 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. less thanbrgreater than less thanbrgreater thanOutcome 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. less thanbrgreater than less thanbrgreater thanResults 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. less thanbrgreater than less thanbrgreater thanConclusions: 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.

Place, publisher, year, edition, pages
Elsevier, 2013. Vol. 63, no 3, 551-560 p.
Keyword [en]
Antifibrotic, Collagen III, Elastin, Immunohistochemistry, Mesenchymal stromal cells, Polymerase chain reaction, Stem cells, Tunica albuginea, Transforming growth factor beta, Western blot
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-89507DOI: 10.1016/j.eururo.2012.09.034ISI: 000314107100033OAI: diva2:608384

Funding Agencies|European Society for Sexual Medicine (ESSM)||Urological Research Institute, Milan, Italy||FWO||

Available from: 2013-02-27 Created: 2013-02-26 Last updated: 2013-03-11

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Hedlund, Petter
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Clinical PharmacologyFaculty of Health SciencesDepartment of Clinical Pharmacology
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