Intratunical Injection of Human Adipose Tissue-Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie's Disease

Fabio Castiglione; Petter Hedlund; Emanuel Weyne; Lukman Hakim; Francesco Montorsi; Trinity J Bivalacqua; Dirk De Ridder; Uros Milenkovic; David Ralph; Giulio Garaffa; Asif Muneer; Steven Joniau; Maarten Albersen; Trauma and Reconstructive Urology Working Party of the European Association of Urology Young Academic Urologists

doi:10.1016/j.esxm.2018.09.003

Intratunical Injection of Human Adipose Tissue-Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie's Disease

Sex Med. 2019 Mar;7(1):94-103. doi: 10.1016/j.esxm.2018.09.003. Epub 2018 Nov 30.

Authors

Affiliations

¹ Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium; The Institute of Urology, University College of London Hospital, London, UK; Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
² Department of Clinical and Experimental Pharmacology, Lund University, Sweden; Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Sweden. Electronic address: petter.hedlund@lu.se.
³ Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
⁴ Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium; Department of Urology, Airlangga University/Dr Soetomo General Hospital, Surabaya, Indonesia.
⁵ Division of Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
⁶ The James Buchanan Brady Urological Institute, Department of Urology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
⁷ The Institute of Urology, University College of London Hospital, London, UK.
⁸ The Institute of Urology, University College of London Hospital, London, UK; Division of Surgery and Interventional Science, National Institute for Health Research Biomedical Research Centre, University College London Hospital, London, UK.

Abstract

Introduction: Previous studies have shown that the injection of adipose tissue-derived stem cells (ADSCs) into the tunica albuginea (TA) during the active phase of Peyronie's disease (PD) prevents the development of fibrosis.

Aim: To investigate, using an animal model, whether local injection of human ADSCs (hADSCs) can alter the degree of fibrosis in the chronic phase of PD.

Methods: 27 male, 12-week-old rats were divided into 3 equal groups: sham, PD without treatment, and PD treated with hADSCs 1 month after disease induction. Sham rats underwent 2 injections of vehicle into the TA 1 month apart. PD rats underwent transforming growth factor β1 (TGFβ1) injection and injection of vehicle 1 month later. PD-hADSC rats underwent TGFβ1 injection followed by 1 million hADSCs 1 month later. 1 week after treatment, n = 3 animals/group were euthanized, and the penises were harvested for quantitative polymerase chain reaction. 1 month after treatment, the other animals, n = 6 per group, underwent measurement of intracavernous pressure (ICP) and mean arterial pressure (MAP) during electrostimulation of the cavernous nerve. After euthanasia, penises were again harvested for histology and Western blot.

Main outcome measure: The primary outcome measures included (a) gene expression at one week post-injection; (b) measurement of ICP/MAP upon cavernous nerve stimulation as a measure of erectile function; (c) elastin, collagen I and III protein expression; and (d) Histomorphometric analysis of the penis. Means where compared by analysis of variance (ANOVA) followed by a Student-Newman-Keuls test for post hoc comparisons or Mann-Whitney test when applicable.

Results: No significant difference was noted in ICP or ICP/MAP in response to cavernous nerve electrostimulation between the 3 groups at 2.5, 5, and 7.5 V (P > .05 for all voltages). PD animals developed tunical and subtunical areas of fibrosis with a significant upregulation of collagen III protein. The collagen III/I ratio was higher in the PD (4.6 ± 0.92) group compared with sham (0.66 ± 0.18) and PD-hADSC (0.86 ± 0.06) groups (P < .05) These fibrotic changes were prevented when treated with hADSCs. Compared with PD rats, PD-hADSC rats demonstrated a decreased expression of several fibrosis-related genes.

Conclusion: Injection of hADSCs reduces collagen III expression in a rat model of chronic PD. Castiglione F, Hedlund P, Weyne E, et al. Intratunical Injection of Human Adipose Tissue-Derived Stem Cells Restores Collagen III/I Ratio in a Rat Model of Chronic Peyronie's Disease. Sex Med 2019;7:94-103.

Keywords: Adipose Stem Cell; Fibrosis; Peyronie’s Disease; Stem Cell.