Therapeutic Potential of Adipose-derived Stem Cell-based Microtissues in a Rat Model of Stress Urinary Incontinence

Therapeutic Potential of Adipose-derived Stem Cell-based Microtissues in a Rat Model of Stress Urinary Incontinence
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脂肪干细胞微组织在压力性尿失禁大鼠模型中的治疗潜力

DOI:
10.1016/j.urology.2016.08.009
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发表时间:
2016-11-01
期刊:
影响因子:
2.1
通讯作者:
Xin, Zhongcheng
Xin, Zhongcheng
中科院分区:
医学4区
文献类型:
--
作者:
Li, Meng;Li, Guangyong;Xin, Zhongcheng

文献摘要

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目的探讨脂肪干细胞(adipose-derived stem cells,ADSCs)三维培养治疗压力性尿失禁(stress urinary incontinence,SUI)的可能性及其机制。48只SD大鼠经阴道扩张4 h后行双侧卵巢切除术建立SUI模型。10只大鼠接受假卵巢切除术而不扩张阴道作为对照组。将SUI大鼠分为3组,分别经尿道注射磷酸盐缓冲液、ADSCs和MT。在注射后第1、3、7和28天(n = 3)收获标本用于组织学检查和ADSC追踪。在第28天,检查剩余大鼠的排尿功能。结果MT组排尿功能恢复较ADSC组好,组织病理学结构恢复较ADSC组好。与ADSC相比,MTs在体外表达更高水平的血管内皮生长因子和TNF α刺激基因/蛋白6,在体内表现出更高的留存率。(C)2016 Elsevier Inc.
OBJECTIVE To examine the potential and mechanism of 3-dimensional cultures of adipose-derived stem cells (ADSCs) in the treatment of stress urinary incontinence (SUI) in a rat model simulating menopause combined with preceding childbirth injury.MATERIALS AND METHODS ADSCs were used to generate microtissues (MTs) with a hanging drop method. Forty-eight postpartum Sprague-Dawley rats were developed as SUI models after 4 hours of vagina dilation followed by bilateral ovariectomy. Ten rats that underwent sham ovariectomy without vagina dilation served as the control group. The SUI rats were divided into 3 groups and received urethral injection of phosphate-buffered saline, ADSCs, and MTs. Specimens were harvested for histology examination and ADSCs tracking at days 1, 3, 7, and 28 (n = 3) postinjection. At day 28, the remaining rats were examined for voiding function. Western blot, immunofluorescence, and immunohistochemistry staining were performed to examine histological changes and cytokine expression.RESULTS The voiding function and histopathological structures were better recovered in the MT group than in the ADSC group. Compared with ADSCs, MTs express higher level of vascular endothelial growth factor and TNF alpha-stimulated gene/protein 6 in vitro, and represented a higher retention rate in vivo.CONCLUSION Urethral injection of MTs better restored voiding function than ADSCs. (C) 2016 Elsevier Inc.