Autologous bone-marrow-derived mesenchymal stem cell transplantation into injured rat urethral sphincter

Yoshiaki Kinebuchi, Naoki Aizawa, Tetsuya Imamura, Osamu Ishizuka, Yasuhiko Igawa, Osamu Nishizawa
International Journal of Urology: Official Journal of the Japanese Urological Association 2010, 17 (4): 359-68

OBJECTIVES: To evaluate the functional and histological recovery by autologous bone-marrow-derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters.

METHODS: BMSC were harvested from female Sprague-Dawley retired breeder rats for later transplantation. The cells were cultured, and transfected with the green fluorescence protein gene. The urethral sphincters were injured by combined urethrolysis and cardiotoxin injection. One week after injury, the cultured BMSC were injected autologously into the periurethral tissues. Controls included sham-operated rats and injured rats injected with cell-free medium (CFM). Abdominal leak point pressures (LPP) were measured before and after surgery during the following 13 weeks. The urethras were then retrieved for histological evaluation. The presence of green-fluorescence-protein-labeled cells and the regeneration of skeletal muscles, smooth muscles, and peripheral nerves were evaluated by immunohistochemical staining.

RESULTS: LPP was significantly reduced in the injured rats. It increased gradually after transplantation, but there was no significant difference between the BMSC and CFM groups. In the BMSC group, transplanted cells survived and differentiated into striated muscle cells and peripheral nerve cells. The proportions of skeletal muscle cells and peripheral nerves in the urethra were significantly greater in the BMSC group compared to the CFM group.

CONCLUSIONS: Despite a clear trend towards recovery of LPP in BMSC-transplanted urethras, no significant effect was detected. Further study is required for clinical applications for the treatment of stress urinary incontinence.

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