Fate of implanted syngenic muscle precursor cells in striated urethral sphincter of female rats: perspectives for treatment of urinary incontinence

Abstract

Objectives: To analyze the outcome of syngenic skeletal muscle precursor cells (MPCs) after implantation in the striated urethral sphincter of the female rat.

Methods: MPCs were isolated from the striated muscles of the lower limbs and infected with a retrovirus carrying the gene for green fluorescent protein. Approximatively 10(5) cells were injected longitudinally in the striated urethral sphincter of 24 animals using a 10-muL Hamilton syringe. The whole urethra was excised at 0, 1, 7, 10, 14, 30, and 90 days after implantation for histologic study and fluorescence analysis of the transections.

Results: At days 0 and 1, some small, round, fluorescent MPCs were observed at the injection site. At day 7, significant MPC persistence was noted, with infiltration of inflammatory cells in the whole urethral wall (striated muscle layer, smooth muscle layer, and connective tissue). At day 10, some fusiform cells appeared in the striated muscle layer, suggesting the incorporation of MPCs into the striated myofibers. Inflammatory cells were no longer visible. At day 14, the fusiform cells tended to be larger. The small, round cells were no longer seen. At days 30 and 90, all myofibers of the striated muscle layer were strongly fluorescent, and no fluorescence was detectable in the smooth muscle layer.

Conclusions: Implantation of skeletal MPCs in the urethral sphincter resulted in selective incorporation into striated myofibers. Muscle-derived cell autografting could represent a new approach for the treatment of urinary incontinence in humans.