Regulation of Growth and Differentiation of Human Urethral Rhabdosphincter Cells

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Regeneration of urethral rhabdosphincter muscle will be a new possible therapy for urinary stress incontinence. We selectively cultured skeletal satellite cells from human urethral rhabdosphincter using neural cell adhesion molecule as a cell surface marker. Proliferation of satellite cells of urethral rhabdosphincter is enhanced by growth factors such as hepatocyte growth factor(HGF) and insulin-like growth factor-I(IGF-I) via MAPK and PI3-K signaling pathways, respectively. As the satellite cells produced both HGF and IGF-I and the neutralizing antibodies against HGF and IGF-I inhibited the growth, these growth factors stimulate the growth of the urethral rhabdosphincter cells as autocrine frashion. These findings suggest that local injections of HGF and IGF-I around membranous urethra may be useful to regenerate urethral rhabdosphincter to treat stress incontinence.