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
相关论文
共 50 条
  • [31] Human adipose tissue-derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma
    Altanerova, Veronika
    Cihova, Marina
    Babic, Michal
    Rychly, Boris
    Ondicova, Katarina
    Mravec, Boris
    Altaner, Cestmir
    INTERNATIONAL JOURNAL OF CANCER, 2012, 130 (10) : 2455 - 2463
  • [32] Culture-expanded allogenic adipose tissue-derived stem cells attenuate cartilage degeneration in an experimental rat osteoarthritis model
    Mei, Li
    Shen, Bojiang
    Ling, Peixue
    Liu, Shaoying
    Xue, Jiajun
    Liu, Fuyan
    Shao, Huarong
    Chen, Jianying
    Ma, Aibin
    Liu, Xia
    PLOS ONE, 2017, 12 (04):
  • [33] Human Adipose Tissue Derived Stem Cells Promote Liver Regeneration in a Rat Model of Toxic Injury
    Koellensperger, Eva
    Niesen, Willem
    Kolbenschlag, Jonas
    Gramley, Felix
    Germann, Guenter
    Leimer, Uwe
    STEM CELLS INTERNATIONAL, 2013, 2013
  • [34] Efficacy of combination therapy with pentosan polysulfate sodium and adipose tissue-derived stem cells for the management of interstitial cystitis in a rat model
    Kim, Bum Soo
    Chun, So Young
    Lee, Eun Hye
    Chung, Jae-Wook
    Lee, Jun Nyung
    Ha, Yun-Sok
    Choi, Jae Young
    Song, Phil Hyun
    Kwon, Tae Gyun
    Han, Man-Hoon
    Kim, Dae Hwan
    Yoo, Eun Sang
    STEM CELL RESEARCH, 2020, 45
  • [35] Cotransplantation of Mouse Neural Stem Cells (mNSCs) With Adipose Tissue-Derived Mesenchymal Stem Cells Improves mNSC Survival in a Rat Spinal Cord Injury Model
    Oh, Jin Soo
    Kim, Keung Nyun
    An, Sung Su
    Pennant, William A.
    Kim, Hyo Jin
    Gwak, So-Jung
    Yoon, Do Heum
    Lim, Mi Hyun
    Choi, Byung Hyune
    Ha, Yoon
    CELL TRANSPLANTATION, 2011, 20 (06) : 837 - 849
  • [36] Adipose tissue-derived mesenchymal stem cells have better restorative capacity than bone marrow-derived cells in a cerebellar ataxic rat model
    Atta, Rasha M.
    Ameen, Angie M.
    Korayem, Horeya Erfan
    Abogresha, Noha
    El-Wazir, Yasser
    ARCHIVES OF MEDICAL SCIENCE, 2025, 21 (01) : 298 - 312
  • [37] Transplantation of Human Adipose Tissue-Derived Stem Cells Delays Clinical Onset and Prolongs Life Span in ALS Mouse Model
    Kim, Kwang S.
    Lee, Hong J.
    An, Jin
    Kim, Yun B.
    Ra, Jung Chan
    Lim, Inja
    Kim, Seung U.
    CELL TRANSPLANTATION, 2014, 23 (12) : 1585 - 1597
  • [38] The Role of Chemokines in Proangiogenic Action Induced by Human Adipose Tissue-Derived Mesenchymal Stem Cells in the Murine Model of Hindlimb Ischemia
    Cho, Hyun Hwa
    Kim, Yeon Jeong
    Kim, Jong Tae
    Song, Ji Sun
    Shin, Keun Koo
    Bae, Yong Chan
    Jung, Jin Sup
    CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2009, 24 (5-6) : 511 - 518
  • [39] Physical exercise and human adipose-derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson's disease
    Cucarian, Jaison D.
    Berrio, Jenny P.
    Rodrigues, Cristiano
    Zancan, Mariana
    Wink, Marcia R.
    de Oliveira, Alcyr
    JOURNAL OF NEUROSCIENCE RESEARCH, 2019, 97 (09) : 1095 - 1109
  • [40] Recruitment of Intracavernously Injected Adipose-Derived Stem Cells to the Major Pelvic Ganglion Improves Erectile Function in a Rat Model of Cavernous Nerve Injury
    Fandel, Thomas M.
    Albersen, Maarten
    Lin, Guiting
    Qiu, Xuefeng
    Ning, Hongxiu
    Banie, Lia
    Lue, Tom F.
    Lin, Ching-Shwun
    EUROPEAN UROLOGY, 2012, 61 (01) : 201 - 210