Bone Marrow Mesenchymal Stromal Cell Therapy for External Urethral Sphincter Restoration in a Rat Model of Stress Urinary Incontinence

作者：Corcos Jacques^*; Loutochin Oleg; Campeau Lysanne; Eliopoulos Nicoletta; Bouchentouf Manaf; Blok Bertil; Galipeau Jacques

来源：Neurourology and Urodynamics, 2011, 30(3): 447-455.

DOI：10.1002/nau.20998

• bone marrow mesenchymal stromal cells
• calponin
• desmin
• external urethral sphincter deficiency
• leak point pressure measurement
• regenerative medicine
• SMA
• stress urinary incontinence

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). Materials and 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 alpha-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 cmH2O in rats implanted with MSCs and 16.21 +/- 1.26 cmH2O in SUI controls (P < 0.001). Atrophic urethras with implanted MSCs were positively stained for myosin heavy chain and desmin. Conclusion: 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. Neurourol. Urodynam. 30: 447- 455, 2011.

• 出版日期2011
• 单位河北医科大学