Journal Article

Longitudinal Pilot Study of Progressive Urethral Sub-Obstruction in a Canine Model: Bladder Functional and Structural Changes and Exploratory Evaluation of Autologous Mesenchymal Stem Cells

Porato, Mathilde, Antoine, Nadine, de Leval, Jean, Pincemail, Joël, Noël, Stéphanie, Bolen, Géraldine, Piret, Joëlle, Hamaide, Annick, Garigliany, Mutien-Marie, Decortis, Frédéric

2026

Overview

Bladder outlet obstruction (BOO) may lead to detrusor decompensation through progressive bladder remodeling. Most experimental studies rely on acutely induced BOO in rodents. Since progressive obstruction better reflects the condition, non-lethal models are needed to investigate chronic obstruction pathophysiology and evaluate regenerative therapies. This exploratory study aimed to evaluate (1) a progressive BOO model induced by an artificial urethral sphincter (AUS) in 2 dogs and (2) the systemic administration of autologous adipose-derived mesenchymal stem cells (ADMSCs) after obstruction release. Two intact male dogs underwent progressive BOO through gradual AUS inflation. Longitudinal assessment included telemetric urodynamic monitoring, urethral pressure profilometry, ultrasonography, post-void residual measurement, oxidative stress markers in serial blood samples and serial bladder biopsies for histology, transmission electron microscopy, immunohistochemistry, RT-qPCR and RNA sequencing (CCL2, CCR2, GFAP, VEGF, HGF). After AUS removal, one dog received three intravenous injections of 20 × 106 PKH26-labelled autologous ADMSCs. BOO induced functional changes (increased detrusor pressure and urethral resistance, decreased urinary flow, prolonged voiding). No detrusor decompensation or fibrosis comparable to the human condition developed, encouraging refinement of this model. ADMSCs appeared to reach the bladder wall safely, but any influence on the glutathione redox system and CCL2 protein expression needs to be confirmed.

• Publisher: MDPI AG,Multidisciplinary Digital Publishing Institute (MDPI)
• Subject: Analysis / Animal models / Biopsy / Bladder / canine / Cell therapy / Dogs / Fibrosis / Glial fibrillary acidic protein / Glutathione / Histology / Hypoxia / Immunohistochemistry / immunostaining / Laboratories / Life sciences / Mesenchymal stem cells / Methadone / Monocyte chemoattractant protein 1 / Morphology / Médecine vétérinaire & santé animale / Oxidative stress / Pilot projects / Prostate / Quality of life / RNA expression / Sciences du vivant / Smooth muscle / Sphincter / Stem cells / Structure-function relationships / telemetry / Transmission electron microscopy / Transplantation / urethral obstruction / Urinalysis / urinary bladder / Urine / urodynamics / Urogenital system / Vascular endothelial growth factor / Veterinary (all) / Veterinary medicine & animal health