Kwon Dongdeuk, Kim Yongtae, Pruchnic Ryan, Jankowski Ron, Usiene Irma, de Miguel Fernando, Huard Johnny, Chancellor Michael B
Department of Urology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Urology. 2006 Aug;68(2):449-54. doi: 10.1016/j.urology.2006.03.040.
To compare muscle-derived cells (MDCs) and fibroblasts with regard to their potential for restoration of urethral function on injection in a previously established animal model of stress urinary incontinence.
The animals were divided into four (dosage) or five (cell concentration) experimental groups: normal, nontreated controls (normal group) or bilateral sciatic nerve transection with either periurethral injection of saline (saline group), MDCs (MDC group), fibroblasts (fibroblast group), or MDC/fibroblast mixture (mixed group). At 4 weeks after injection, the leak point pressure (LPP) was measured and contractility testing and histologic analysis were performed.
The histologic examination demonstrated muscular atrophy in the saline group and new striated muscle fibers at the sites of MDC injection in the MDC group, but not in the fibroblast group. Denervation of the urethra resulted in a significant decrease of maximal fast-twitch muscle contraction amplitude to only 9% of normal. MDC injection into the denervated urethra significantly improved the fast-twitch muscle contraction amplitude to 73% of normal. The LPP of the normal, saline, MDC, fibroblast, and mixed groups at 4 weeks after treatment was 43.3 +/- 2.5, 25.8 +/- 1.4, 38.2 +/- 4.2, 38.3 +/- 1.2, and 34.5 +/- 3.3 cm H2O, respectively. In the cell dosage experiment, the LPP increased with increases in the injected cell number. Evidence of obstruction was observed in the high-dose (1 x 10(7) cells) fibroblast group.
Although both MDCs and fibroblast injection increased the LPP in a stress urinary incontinence rat model, only MDCs significantly improved urethral muscle strip contractility. Moreover, urinary retention developed with high-dose fibroblast injection, but not with MDC injection.
在先前建立的压力性尿失禁动物模型中，比较肌肉衍生细胞（MDCs）和成纤维细胞注射后恢复尿道功能的潜力。
将动物分为四个（剂量）或五个（细胞浓度）实验组：正常、未处理的对照组（正常组），或双侧坐骨神经横断后在尿道周围注射生理盐水（生理盐水组）、MDCs（MDC组）、成纤维细胞（成纤维细胞组）或MDC/成纤维细胞混合物（混合组）。注射后4周，测量漏点压力（LPP），并进行收缩性测试和组织学分析。
组织学检查显示，生理盐水组出现肌肉萎缩，MDC组在MDC注射部位有新的横纹肌纤维形成，而成纤维细胞组未出现。尿道去神经支配导致最大快肌收缩幅度显著降低，仅为正常的9%。向去神经支配的尿道注射MDC可使快肌收缩幅度显著提高至正常的73%。治疗后4周，正常组、生理盐水组、MDC组、成纤维细胞组和混合组的LPP分别为43.3±2.5、25.8±1.4、38.2±4.2、38.3±1.2和34.5±3.3 cm H2O。在细胞剂量实验中，LPP随注射细胞数量的增加而增加。在高剂量（1×10⁷个细胞）成纤维细胞组中观察到梗阻迹象。
虽然在压力性尿失禁大鼠模型中，注射MDCs和成纤维细胞均增加了LPP，但只有MDCs显著改善了尿道肌条的收缩性。此外，高剂量注射成纤维细胞会导致尿潴留，而注射MDCs则不会。
