Regeneration of the Pelvic and Urethral Supports by Muscle Derived Stem Cells

描述（由申请人提供）：最近的证据表明盆腔肌肉的功能损害或萎缩，如提肛肌、尿道支撑和尿道括约肌，是女性压力性尿失禁（SUI）的原因。SUI是一种常见的疾病，发病率很高，治疗方法包括盆底运动、药物治疗和手术。目前，手术治疗是真正SUI的主要治疗方法，治愈率最高。然而，它们是侵入性的，并伴有术中和术后并发症。因此，需要不断寻找治疗SUI的更好方法。以肌肉来源的成体干细胞（肌肉来源的干细胞，MDSC）为基础的细胞疗法有望实现组织修复，最终目标是再生和恢复骨盆支持膀胱、尿道和尿道的正常功能。近年来，成体干细胞移植已被证明可以再生萎缩或损伤的骨骼肌肌纤维。平滑肌再生也已得到证实。成体干细胞移植用于修复导致SUI的缺陷组织是一种新颖而有前途的治疗方法。

DESCRIPTION (provided by applicant): Recent evidence demonstrates that the functional impairment or atrophy of pelvic muscles, such as levator ani, urethral supports and urethral sphincter, are responsible for stress urinary incontinence (SUI) in women. SUI is a common condition with significant morbidity, and treatment options include pelvic floor exercises, pharmacological treatment, and surgery. Currently, surgical management is the main treatment of genuine SUI and offers the highest cure rates. However, they are invasive and associated with complications, both intra- and post-operatively. There is, therefore, a constant search for a better approach to treat SUI. Cell-based therapies with adult stem cells of muscle origin (muscle-derived stem cells, MDSC) hold promise for tissue repair with the ultimate goal to regenerate and restore normal function of the pelvic support to the bladder, urethrovesical junction, and urethra. In recent years, adult stem cell implantation has been shown to regenerate myofibers in atrophic or injured skeletal muscle. Regeneration of smooth muscle has also been demonstrated. Adult stem cell implantation for the repair of defective tissues responsible for SUI is a novel and promising option for a therapy of this condition. Our overall goal of this study is to investigate, in a rat model, whether the implantation of autologous muscle-derived stem cells into the atrophic levator ani, with or without concurrent implantation into the striated urogenital sphincter or urethral smooth muscles, can reverse the atrophy and subsequently improve or cure SUI. The long-term objective is to eventually devise a clinical trial for the use of autologous stem cells in women for the correction of SUI. This study involves two aims. The first aim involves the in vitro isolation, purification, and characterization of rat muscle derived stem cells. The outcomes will include the determination of myotube formation, smooth muscle cell differentiation, and myofibroblast formation. These tests will determine whether the ongoing cell culture is still active in generating skeletal and smooth muscles in the absence of myofibroblasts. The second aim is to determine the effects of implanting autologous stem cells into the atrophic levator ani of female rats, with or without concurrent implantation into the striated urogenital sphincter or urethral smooth muscles. The outcomes include urodynamic measurements, stress test, skeletal muscle weight, fate of the implanted stem cells, and cell lineage determination.