Furuta Akira, Jankowski Ron J, Honda Masashi, Pruchnic Ryan, Yoshimura Naoki, Chancellor Michael B
Department of Urology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Neurourol Urodyn. 2007;26(7):966-71. doi: 10.1002/nau.20448.
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.
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.
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.
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.
本综述旨在探讨：1）神经生理学，强调尿道中段的重要性以及压力性尿失禁（SUI）的治疗；2）当前用于微创治疗的可注射细胞来源；3）肌肉衍生干细胞（MDSCs）递送神经营养因子的潜力。
使用以下主题词组合在PUBMED上进行检索：尿失禁、尿道括约肌、干细胞、肌肉、脂肪、神经营养蛋白。此外，我们将更新我们实验室的最新研究成果。
在人和动物尿道的解剖学和功能研究中，包含横纹括约肌的尿道中段对于维持控尿至关重要。基于细胞的治疗通常与使用自体多能干细胞相关，例如骨髓基质细胞。然而，采集骨髓基质干细胞困难、痛苦，并且处理后获得的干细胞数量可能较少。相比之下，替代的自体成体干细胞，如MDSCs和脂肪衍生干细胞，可以轻松大量获取且不适感最小。并非所有细胞治疗都是相同的，肌肉来源的MDSCs与成肌细胞和成纤维细胞在安全性和有效性方面的差异就证明了这一点。
移植的干细胞可能具有自我更新和多能分化的能力，从而导致括约肌再生。此外，此类细胞可能释放或经改造后释放神经营养因子，随后通过旁分泌招募内源性宿主细胞，以协同促进神经整合肌肉的再生反应。SUI治疗新范式的曙光可能即将到来。
