Adipose-derived Stem Cells Counteract Urethral Stricture Formation in Rats.

Abstract

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.

• Authors: Fabio Castiglione, Karel Dewulf, Lukman Hakim, Emmanuel Weyne, Francesco Montorsi, Andrea Russo, Luca Boeri, Trinity J Bivalacqua, Dirk De Ridder, Steven Joniau, Maarten Albersen, Petter Hedlund
• Journal: European urology (Eur Urol) Vol. 70 Issue 6 Pg. 1032-1041 (12 2016) ISSN: 1873-7560 [Electronic] Switzerland
• PMID: 27156445 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Chemical References

• Transforming Growth Factor beta1
• Collagen
• Elastin
• Nitric Oxide Synthase Type II
• Nitric Oxide Synthase Type III
• Nos2 protein, rat
• Nos3 protein, rat

Topics

• Adipose Tissue (cytology)
• Animals
• Blotting, Western
• Collagen (drug effects, metabolism)
• Disease Models, Animal
• Elastin (drug effects, metabolism)
• Fibrosis
• Humans
• Male
• Nitric Oxide Synthase Type II (drug effects, metabolism)
• Nitric Oxide Synthase Type III (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Stem Cell Transplantation
• Transforming Growth Factor beta1 (pharmacology)
• Urethra (drug effects, metabolism, pathology)
• Urethral Stricture (prevention & control)
• Urination
• Urodynamics