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Intratunical Injection of Human Adipose Tissue-Derived Stem Cells Restores Collagen III/IRatio in a Rat Model of Chronic Peyronies Disease
Univ Leuven, Belgium; Univ Coll London Hosp, England; IRCCS Osped San Raffaele, Italy.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pharmacology. Lund Univ, Sweden.
Univ Leuven, Belgium.
Univ Leuven, Belgium; Airlangga Univ, Indonesia.
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2019 (English)In: SEXUAL MEDICINE, ISSN 2050-1161, Vol. 7, no 1, p. 94-103Article in journal (Refereed) Published
Abstract [en]

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 Peyronies 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 beta 1 (TGF beta 1) injection and injection of vehicle 1 month later. PD-hADSC rats underwent TGF beta 1 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 (Pamp;gt;.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 (Pamp;lt;.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. Copyright (C) 2018, International Society for Sexual Medicine. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Place, publisher, year, edition, pages
ELSEVIER SCI LTD , 2019. Vol. 7, no 1, p. 94-103
Keywords [en]
Peyronies Disease; Stem Cell; Adipose Stem Cell; Fibrosis
National Category
Otorhinolaryngology
Identifiers
URN: urn:nbn:se:liu:diva-155557DOI: 10.1016/j.esxm.2018.09.003ISI: 000460015200013PubMedID: 30503767OAI: oai:DiVA.org:liu-155557DiVA, id: diva2:1299385
Note

Funding Agencies|European Society for Sexual Medicine (ESSM); European Urological Scholarship Programme (EUSP); NIHR Biomedical Research Centre, University College London Hospital

Available from: 2019-03-26 Created: 2019-03-26 Last updated: 2019-10-01

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