Advanced Platform Technology Center, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio.
Biomedical Engineering Department, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Am J Physiol Renal Physiol. 2019 Oct 1;317(4):F1047-F1057. doi: 10.1152/ajprenal.00173.2019. Epub 2019 Aug 14.
Stress urinary incontinence (SUI) is more prevalent among women who deliver vaginally than women who have had a cesarean section, suggesting that tissue repair after vaginal delivery is insufficient. A single dose of mesenchymal stem cells (MSCs) has been shown to partially restore urethral function in a model of SUI. The aim of the present study was to determine if increasing the number of doses of MSCs improves urethral and pudendal nerve function and anatomy. We hypothesized that increasing the number of MSC doses would accelerate recovery from SUI compared with vehicle treatment. Rats underwent pudendal nerve crush and vaginal distension or a sham injury and were treated intravenously with vehicle or one, two, or three doses of 2 × 10 MSCs at 1 h, 7 days, and 14 days after injury. Urethral leak point pressure testing with simultaneous external urethral sphincter electromyography and pudendal nerve electroneurography were performed 21 days after injury, and the urethrovaginal complex and pudendal nerve were harvested for semiquantitative morphometry of the external urethral sphincter, urethral elastin, and pudendal nerve. Two and three doses of MSCs significantly improved peak pressure; however, a single dose of MSCs did not. Single, as well as repeated, MSC doses improved urethral integrity by restoring urethral connective tissue composition and neuromuscular structures. MSC treatment improved elastogenesis, prevented disruption of the external urethral sphincter, and enhanced pudendal nerve morphology. These results suggest that MSC therapy for postpartum incontinence and SUI can be enhanced with multiple doses.
压力性尿失禁（SUI）在阴道分娩的女性中比剖宫产的女性更为常见，这表明阴道分娩后的组织修复不足。单次剂量的间充质干细胞（MSCs）已被证明可部分恢复 SUI 模型中的尿道功能。本研究旨在确定增加 MSCs 剂量是否可以改善尿道和阴部神经的功能和解剖结构。我们假设增加 MSC 剂量的次数会比载体治疗更快地恢复 SUI。大鼠接受阴部神经挤压和阴道扩张或假损伤，并在损伤后 1 小时、7 天和 14 天静脉注射载体或 1、2 或 3 剂 2×10 MSCs。损伤后 21 天进行尿道漏点压力测试，同时进行尿道外括约肌肌电图和阴部神经电神经图检查，并采集尿道阴道复合体和阴部神经进行尿道外括约肌、尿道弹性蛋白和阴部神经的半定量形态计量学分析。两剂和三剂 MSCs 可显著提高峰值压力；然而，单剂 MSCs 则不然。单次和重复的 MSC 剂量可通过恢复尿道结缔组织组成和神经肌肉结构来改善尿道完整性。MSC 治疗可改善弹性生成，防止尿道外括约肌破裂，并增强阴部神经形态。这些结果表明，多次剂量的 MSC 治疗可增强产后尿失禁和 SUI 的治疗效果。
