Login to Access Video or Poster Abstract: MP42-07
Sources of Funding: NIH/NIDDK DK079184

Introduction

Removal and injury of rhabdosphincter muscle during prostatectomy surgery is a leading cause of stress urinary incontinence (SUI, 44%), which critically impacts patient mental and physical health. With current treatments, including implantation of artificial urinary sphincter, continence pad use is needed and device failure, erosion of the urethra and infection are significant side effects. Thus a critical unmet need exists to develop novel methods to regenerate rhabdosphincter muscle. We have identified sonic hedgehog (SHH) as an important regulator of muscle in another urogenital organ, the penis, and have developed innovative peptide amphiphile nanofiber hydrogel delivery of SHH protein to regenerate penile smooth muscle, post prostatectomy. If similar SHH signaling mechanisms regulate rhabdosphincter function, then this technology may be applied to regenerate rhabdosphincter muscle post prostatectomy. We hypothesize that SHH protein is critical for human rhabdosphincter homeostasis and regeneration and have examined this hypothesis in human rhabdosphincter tissue.

Methods

Human rhabdosphincter (n=3) was obtained from patients (n=3) undergoing cystectomy. Trichrome stain and immunohistochemical analysis for SHH pathway was performed.

Results

Trichrome stain showed that human rhabdosphincter is a complex mixture of collagen, muscle and elastin fibers. SHH protein was abundantly expressed in rhabdosphincter muscle. The SHH receptor Patched (PTCH1) was also identified, and strongly stained rhabdosphincter muscle.

Conclusions

The SHH pathway is active in adult human rhabdosphincter muscle, suggesting that similar mechanisms of muscle homeostasis and regeneration are present as in human penis tissue, and thus the previously developed peptide amphiphile nanofiber hydrogel delivery of SHH, may be useful for rhabdosphincter muscle regeneration.

Funding

NIH/NIDDK DK079184