Periurethral cellular injection: Comparison of muscle-derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence

Periurethral cellular injection: Comparison of muscle-derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in an animal model of stress urinary incontinence
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DOI:
10.1016/j.urology.2006.03.040
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发表时间:
2006-08-01
期刊:
影响因子:
2.1
通讯作者:
Chancellor, Michael B.
Chancellor, Michael B.
中科院分区:
医学4区
文献类型:
--
作者:
Kwon, Dongdeuk;Kim, Yongtae;Chancellor, Michael B.

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目标.比较肌源性细胞(MDCs)和成纤维细胞在先前建立的应激性尿失禁动物模型中注射后恢复尿道功能的潜力。将动物分为4个(剂量)或5个(细胞浓度)实验组:正常对照组、未处理对照组(正常组)或双侧坐骨神经横断,尿道周围注射生理盐水(生理盐水组)、MDC(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,测量漏尿点压(LPP),并进行收缩试验和组织学分析。组织学检查显示生理盐水组的肌肉萎缩,MDC组的MDC注射部位有新的横纹肌纤维,而成纤维细胞组没有。尿道去神经导致最大快缩肌收缩幅度显著降低,仅为正常的9%。将MDC注射到失神经支配的尿道中显著改善了快缩肌收缩幅度,达到正常的73%。处理后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随着注射细胞数量的增加而增加。在高剂量(11 x 10(7)个细胞)成纤维细胞组中观察到阻塞的证据。虽然MDCs和成纤维细胞注射增加压力性尿失禁大鼠模型的LPP,只有MDCs显着改善尿道肌条收缩。此外,尿潴留发生与高剂量的成纤维细胞注射,而不是与MDC注射。
Objectives. 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.Methods. 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.Results. 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 (11 x 10(7) cells) fibroblast group.Conclusions. 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.