AIMS: This review aims to discuss: 1) the neurophysiology, highlighting the importance of the middle urethra, and treatment of stress urinary incontinence (SUI); 2) current injectable cell sources for minimally-invasive treatment; and 3) the potential of muscle-derived stem cells (MDSCs) for the delivery of neurotrophic factors. METHODS: A PUB-MED search was conducted using combinations of heading terms: urinary incontinence, urethral sphincter, stem cells, muscle, adipose, neurotrophins. In addition, we will update the recent work from our laboratory. RESULTS: In anatomical and functional studies of human and animal urethra, the middle urethra containing rhabdosphincter, is critical for maintaining continence. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as the bone marrow stromal cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells upon processing. In contrast, alternative autologous adult stem cells such as MDSCs and adipose-derived stem cells can be easily obtained in large quantities and with minimal discomfort. Not all cellular therapies are the same, as demonstrated by the differences in safety and efficacy from muscle-sourced MDSCs versus myoblasts versus fibroblasts. CONCLUSIONS: Transplanted stem cells may have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. The dawn of a new paradigm in the treatment of SUI may be near. (c) 2007 Wiley-Liss, Inc.
AIMS: This review aims to discuss: 1) the neurophysiology, highlighting the importance of the middle urethra, and treatment of stress urinary incontinence (SUI); 2) current injectable cell sources for minimally-invasive treatment; and 3) the potential of muscle-derived stem cells (MDSCs) for the delivery of neurotrophic factors. METHODS: A PUB-MED search was conducted using combinations of heading terms: urinary incontinence, urethral sphincter, stem cells, muscle, adipose, neurotrophins. In addition, we will update the recent work from our laboratory. RESULTS: In anatomical and functional studies of human and animal urethra, the middle urethra containing rhabdosphincter, is critical for maintaining continence. Cell-based therapies are most often associated with the use of autologous multipotent stem cells, such as the bone marrow stromal cells. However, harvesting bone marrow stromal stem cells is difficult, painful, and may yield low numbers of stem cells upon processing. In contrast, alternative autologous adult stem cells such as MDSCs and adipose-derived stem cells can be easily obtained in large quantities and with minimal discomfort. Not all cellular therapies are the same, as demonstrated by the differences in safety and efficacy from muscle-sourced MDSCs versus myoblasts versus fibroblasts. CONCLUSIONS: Transplanted stem cells may have the ability to undergo self-renewal and multipotent differentiation, leading to sphincter regeneration. In addition, such cells may release, or be engineered to release, neurotrophins with subsequent paracrine recruitment of endogenous host cells to concomitantly promote a regenerative response of nerve-integrated muscle. The dawn of a new paradigm in the treatment of SUI may be near. (c) 2007 Wiley-Liss, Inc.
Authors: Akira Furuta; Ron J Jankowski; Ryan Pruchnic; Shin Egawa; Naoki Yoshimura; Michael B Chancellor Journal: Int Urogynecol J Pelvic Floor Dysfunct Date: 2008-04-18