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

肌肉干细胞对骨盆和尿道支持物的再生

• 批准号: 7600411
• 负责人: Matthew H. Ho
• 金额: $ 14.1万
• 依托单位: CHARLES R. DREW UNIVERSITY OF MED & SCI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-03 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7600411
• 关键词: Animals; Atrophic; Autologous; Behavior Therapy; Bilateral; Bladder; Cell Culture Techniques; Cell Differentiation process; Cell Lineage; Cell Therapy; Clinical Trials; Collagen; Defect; Deposition; Excision; Exercise; Female; Functional disorder; Future; Genitourinary system; Goals; Implant; In Vitro; Measurement; Modeling; Morbidity - disease rate; Muscle; Muscle Fibers; Muscle satellite cell; Muscular Atrophy; Myofibroblast; Natural regeneration; Nerve; Operative Surgical Procedures; Outcome; Pelvic floor structure; Pelvis; Pharmacological Treatment; Process; Rattus; Skeletal Muscle; Smooth Muscle; Smooth Muscle Myocytes; Sphincter; Stem cells; Stress Tests; Stress Urinary Incontinence; Surgical Management; Testing; Tissues; Urethra; Urethral sphincter; Urodynamics; Weight; Woman; Wound Healing; adult stem cell; base; functional disability; functional improvement; implantation; improved; injured; interstitial; levator ani muscle; muscle form; muscle regeneration; novel; repaired; satellite cell; skeletal

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.

描述（由申请人提供）：最近的证据表明，骨盆肌肉的功能障碍或萎缩，例如Levator ANI，尿道支撑和尿道括约肌，是女性的压力尿失禁（SUI）。 SUI是一种常见的疾病，具有明显的发病率，治疗方案包括骨盆底运动，药理学治疗和手术。目前，手术管理是真正的SUI的主要治疗方法，并提供了最高的治疗率。但是，它们具有侵入性，并且在术后和术后都与并发症有关。因此，人们一直在寻找一种更好的方法来治疗SUI。基于细胞的肌肉起源干细胞（肌肉衍生的干细胞，MDSC）的基于细胞的疗法有望进行组织修复，其最终目标是再生并恢复骨盆支撑对膀胱，尿道交界处和尿道的正常功能。近年来，成年干细胞植入已显示出在萎缩或受伤的骨骼肌中再生肌纤维。平滑肌的再生也已被证明。用于修复负责SUI的有缺陷组织的成年干细胞植入是对这种情况进行治疗的一种新颖而有前途的选择。 这项研究的总体目标是在大鼠模型中调查自体肌肉衍生的干细胞是否植入萎缩性levator ani中，是否有或不同时植入到晶体的尿强生殖器括约肌或尿道平滑肌肉中，都可以逆转萎缩并随后改善或固化SUI。长期目标是最终设计一项临床试验，以用于使用女性自体干细胞进行纠正。这项研究涉及两个目标。第一个目的涉及大鼠肌肉衍生的干细胞的体外分离，纯化和表征。结果将包括测定肌管形成，平滑肌细胞分化和肌纤维细胞的形成。这些测试将确定在没有肌纤维细胞的情况下，正在进行的细胞培养是否仍在产生骨骼和平滑肌。第二个目的是确定将自体干细胞植入雌性大鼠的萎缩性左旋肌，有或不同时植入到条纹的泌尿生殖器括约肌或尿道平滑肌中。结果包括尿动力学测量，应力测试，骨骼肌体重，植入干细胞的命运以及细胞谱系测定。