TY - JOUR
T1 - Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats
AU - Castiglione, Fabio
AU - Dewulf, Karel
AU - Hakim, Lukman
AU - Weyne, Emmanuel
AU - Montorsi, Francesco
AU - Russo, Andrea
AU - Boeri, Luca
AU - Bivalacqua, Trinity J.
AU - De Ridder, Dirk
AU - Joniau, Steven
AU - Albersen, Maarten
AU - Hedlund, Petter
N1 - Funding Information:
Funding/Support and role of the sponsor: This study was fully funded by the Grant Luna 2013 (Societá Italiana di Urologia) awarded to Fabio Castiglione, by the Urological Research Institute, Milan, Italy, the Department of Clinical and Experimental Pharmacology, Lund University, Sweden, and by the Laboratory for Experimental Urology, Gene and Stem Cells Applications, Department of Development and Regeneration, University of Leuven, Leuven, Belgium. The sponsors played no role in the study. Fabio Castiglione is a fellow of the European Urological Scholarship Programme and received an international mobility grant from European Urological Scholarship Programme for this study.
Publisher Copyright:
© 2016 European Association of Urology
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background A medical treatment for urethral stricture (US) is not yet available. Objective To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-β1 in the urethral wall. Intervention One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations US rats exhibited 49–51% shorter micturition intervals, 35–51% smaller micturition volumes and bladder capacity, 33–62% higher threshold pressures and flow pressures, and 35–37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p < 0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34–55% smaller contractions than detrusor from sham rats (p < 0.05). Corresponding values were 11–35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p < 0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p < 0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. Conclusions Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summary Stem cell therapy is effective for preventing urethral stricture in an experimental setting.
AB - Background A medical treatment for urethral stricture (US) is not yet available. Objective To evaluate if local injection of human adipose tissue-derived stem cells (hADSC) prevents urethral fibrosis in a rat model of US. Design, setting, and participants Male rats were divided into three groups: sham, US, and hADSC (n = 12 each). Sham rats received a vehicle injection in the urethral wall. US and hADSCs were incised and injected with the fibrosis-inducer transforming growth factor-β1 in the urethral wall. Intervention One day later, hADSCs were injected in the urethral wall of hADSC rats whereas sham and US rats were injected with the vehicle. After 4 wk, the rats underwent cystometries and tissues were then harvested for functional and molecular analyses. Outcome measurements and statistical analysis Cystometry, microultrasound, histochemistry, organ bath studies, reverse transcription polymerase chain reaction, and western blot. Results and limitations US rats exhibited 49–51% shorter micturition intervals, 35–51% smaller micturition volumes and bladder capacity, 33–62% higher threshold pressures and flow pressures, and 35–37% lower bladder filling compliance compared with hADSC-treated rats and sham rats (p < 0.05). By ultrasound, US rats had hyperechogenic and thick urethral walls with narrowed lumen compared with sham rats, whereas hADSC rats displayed less extensive urethral changes. Isolated detrusor from US rats exhibited 34–55% smaller contractions than detrusor from sham rats (p < 0.05). Corresponding values were 11–35% for isolated detrusors from hADSC rats. Collagen and elastin protein expression were increased in the penile urethras of US rats compared with sham and hADSC groups (p < 0.05). Endothelial and inducible nitric oxide synthase expressions were higher (p < 0.05) in the hADSC group. Compared with US rats, hADSC rats demonstrated decreased expression of several fibrosis-related genes. Administration of hADSCs was performed at an early stage of US development, which we consider a limitation of the study. Conclusions Local injection of hADSCs prevents stricture formation and urodynamic complications in a new rat model for US. Patient summary Stem cell therapy is effective for preventing urethral stricture in an experimental setting.
KW - Animal model
KW - Stem cell
KW - Therapy
KW - Urethral stricture
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U2 - 10.1016/j.eururo.2016.04.022
DO - 10.1016/j.eururo.2016.04.022
M3 - Article
C2 - 27156445
AN - SCOPUS:84964734804
SN - 0302-2838
VL - 70
SP - 1032
EP - 1041
JO - European Urology
JF - European Urology
IS - 6
ER -