Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency
Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency
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DOI：
10.1016/j.urology.2003.10.035
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发表时间：
2004-04-01
期刊：
影响因子：
2.1
通讯作者：
Chancellor, MB
中科院分区：
文献类型：
--
作者：
Chermansky, CJ;Tarin, T;Chancellor, MB
目标。目的：探讨同种异体肌源性细胞(MDCs)能否恢复固有括约肌功能缺陷(ISD)大鼠的括约肌功能。ISD指的是尿道括约肌功能障碍。成年雌性SD大鼠25只，烧灼中尿路外侧组织，造成ISD。烫伤后一周，将1.5×10(6)的MDCs注射到16只大鼠的尿路中部，该细胞是针对β-半乳糖苷酶表达的基因工程细胞。另9只大鼠烧灼后注射Hanks‘s平衡盐液。9只正常大鼠接受假手术作为对照。采用垂直倾斜床/膀胱内压力钳技术测量泄漏点压力(LPP)，对括约肌功能进行研究。用Lacz染色评估MDCs的命运。注射MDCs后，LPP增加，但对膀胱功能无影响。对照组大鼠术后2、4、6周的平均LPP分别为49.8+/-1.3、51.2+/-1.5和51.6+/-2.0 cm H2O。烫伤后2、4、6周和Hanks平衡盐液注射组大鼠LPP分别为17.2±1.4、26.9±1.9和25.5±1.3 cm H2O。烧灼后2周、4周和6周的平均LPP分别为38.2+/-2.2、43.1+/-2.6和51.5+/-0.9 cm H2O。LacZ染色证实MDC已整合到烫伤后尿路的横纹肌层内。尿路内注射MDCs改善了ISD大鼠的括约肌功能，可能为目前的治疗提供了一种有吸引力的替代方案。(C)2004年爱思唯尔公司。
Objectives. To determine whether allogenic muscle-derived cells (MDCs) could restore sphincter function in rats with intrinsic sphincter deficiency (ISD). ISD denotes a malfunction of the urethral sphincter.Methods. ISD was produced in 25 adult female Sprague-Dawley rats by cauterizing tissues lateral to the mid-urethra. One week after cauterization, 1.5 X 10(6) MDCs, genetically engineered for beta-galactosidase expression, was injected into the mid-urethra in 16 rats. Another 9 rats were injected with Hanks' balanced salt solution after cauterization. As a control, 9 normal rats underwent a sham operation. Sphincter function was studied using the vertical tilt table/intravesical pressure clamp technique to measure leak point pressures (LPPs). The fate of the MDCs was assessed using LacZ staining.Results. The injection of MDCs increased the LPP without affecting bladder function. The mean LPP of the control rats 2, 4, and 6 weeks after the sham operation was 49.8 +/- 1.3, 51.2 +/- 1.5, and 51.6 +/- 2.0 cm H2O, respectively. The mean LPP of the rats 2, 4, and 6 weeks after cauterization and Hanks' balanced salt solution injection was 17.2 +/- 1.4, 26.9 +/- 1.9, and 25.5 +/- 1.3 cm H2O, respectively. The mean LPP of the rats 2, 4, and 6 weeks after cauterization and MDC injection was 38.2 +/- 2.2, 43.1 +/- 2.6, and 51.5 +/- 0.9 cm H2O, respectively. LacZ staining confirmed that MDC had integrated within the striated muscle layer of the cauterized urethra.Conclusions. The injection of intraurethral MDCs improved sphincter function in rats with ISD and may provide an attractive alternative to current treatments. (C) 2004 Elsevier Inc.