Identification of Origin and Elucidation of Growth and Differetniation Mechanism of Satellite Cells in Human Urethral Rhabdosphincter

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Objective : Urethral rhabdosphincter is the most important tissue for preservation of urinary continence, and its injury and/or decrease due to aging and prostate surgery induced stress urinary incontinence. This study was performed to clarify and culture satellite cells in human urethral rhabdosphincter for the elucidation of growth and differentiation mechanism and development of new therapeutic modality for urethral rhabdosphincter regeneration.Materials and Method : Human urethral rhabdosphincter was obtained from patients who underwent radical prostatectomy or radical cystoprostatectomy. After the specimens were treated with collagenase and cultured, satellite cells in human urethral rhabdosphincter were isolated by MACS technique using anti-NCAM antibody conjugated with microbeads. Isolated satellite cells were confirmed as striated muscle origin by immunocytochemistry with anti-Myf-5 and anti-MyoD antibodies, and they were transfected with SV40 T antigen to obtain longevity.Results and Conclusion : Satellite cells of human urethral rhabdosphincter produced HGF and IGF-I at mRNA and protein levels, which stimulated their growth. HGF and IGF-I activated MAPK and PI3-K signal transduction in satellite cells of human urethral rhabdosphincter, respectively.Human urethral rhabdosphincter is reported to decrease due to apotosis with aging. In this study, TNF-α induced apoptosis by dose-dependent fashion in satellite cells of human urethral rhabdosphincter for the first time. Inhibitors of TNF-α may protect human urethral rhabdospincter from reduction with aging and be useful for the treatment and prevention of stress urinary incontinence in elderly.