title: Bone marrow mesenchymal stromal cell therapy for external urethral sphincter restoration in a rat model of stress urinary incontinence.
abstract: OBJECTIVE
  To assess the effect of intra-sphincteric injections of bone marrow mesenchymal stromal cells (MSCs) on Valsalva leak point pressure (VLPP) changes in an animal model of stress urinary incontinence (SUI).
  
  
  METHODS
  Twenty-four female Sprague-Dawley rats underwent bilateral pudendal nerve section to induce SUI. Six rats were SUI controls, 6 received periurethral injection of Plasma-Lyte (SUI placebo control) and 12 were given periurethral injection of PKH26-labeled MSCs. Four weeks after injection, conscious cystometry was undertaken in animals and VLPP recorded. All groups were sacrificed, and frozen urethra sections were submitted to pathology and immunohistochemistry assessment.
  
  
  RESULTS
  Rat MSCs were positive for the cell surface antigens CD44, CD73, CD90, and RT1A, and negative for CD31, CD45, and RT1B, confirming their stem cell phenotype. In vitro, differentiated MSCs expressed α-smooth muscle actin (SMA) and desmin, markers of smooth and striated muscles in vivo. Immunohistochemistry of rat urethras revealed PKH26-labeled MSCs in situ and at the injection site. LPP was significantly improved in animals injected with MSCs. Mean LPP was 24.28 ± 1.47 cmH(2) O in rats implanted with MSCs and 16.21 ± 1.26 cmH(2) O in SUI controls (P<0.001). Atrophic urethras with implanted MSCs were positively stained for myosin heavy chain and desmin.
  
  
  CONCLUSIONS
  Rat MSCs have the ability to differentiate and skew their phenotype towards smooth and striated muscles, as demonstrated by SMA up-regulation and desmin expression. Periurethral injection of MSCs in an animal model of SUI restored the damaged external urethral sphincter and significantly improved VLPP.
authors.affiliation: Division of Urology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. jcorcos@uro.jgh.mcgill.ca
authors.forename: Jacques
authors.initials: J
authors.lastname: Corcos
authors.forename: Oleg
authors.initials: O
authors.lastname: Loutochin
authors.forename: Lysanne
authors.initials: L
authors.lastname: Campeau
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Eliopoulos
authors.forename: Manaf
authors.initials: M
authors.lastname: Bouchentouf
authors.forename: Bertil
authors.initials: B
authors.lastname: Blok
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001284:Atrophy; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D007267:Injections; D045164:Mesenchymal Stem Cell Transplantation; D010641:Phenotype; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D013997:Time Factors; D014521:Urethra / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D014550:Urinary Incontinence, Stress / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D014563:Urodynamics
chemical_list: D015415:Biomarkers