Growth mechanism of satellite cells in human urethral rhabdosphincter

Abstract

Aims: To examine the presence of satellite cells in human urethral rhabdosphincter (RS) and to clarify the growth mechanism of these cells.

Methods: Human RS was obtained from patients undergoing radical prostatectomy for prostate cancer. Primary cells were selectively cultured by magnetic affinity cell sorting (MACS) using an anti-neural cell adhesion molecule (NCAM) antibody. Selectively cultured cells, transfected with simian virus-40 T antigen to extend their lifespan, were used for the following experiments: (1) determination of the effects of hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (b-FGF); (2) clarification of the signal transduction pathways used by these growth factors; and (3) examination of the autocrine actions in these cells.

Results: Selectively cultured cells expressed striated muscle markers and could differentiate into myotubes. HGF and IGF-1 stimulated the growth of these cells in a dose-dependent fashion. Regarding signal transduction, HGF phosphorylated ERK1/2 for 120 min while only transiently modifying Akt. In contrast, IGF-1 phosphorylated Akt but not ERK1/2. Furthermore, these cells produced transcripts and proteins for both HGF and IGF-1, and anti-HGF and anti-IGF-1 antibodies suppressed cell proliferation.

Conclusions: Satellite cells are present in human RS. The proliferation of these cells is primarily enhanced through both the endogenous and exogenous actions of HGF and IGF-I via ERK1/2 and Akt. These findings may be useful in the development of a novel technique for the regeneration of human RS to treat urinary incontinence.