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Regenerative medicine based applications to combat stress urinary incontinence

机译:以再生医学为基础的抗压力性尿失禁的应用

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摘要

Stress urinary incontinence (SUI), as an isolated symptom, is not a life threatening condition. However, the fear of unexpected urine leakage contributes to a significant decline in quality of life parameters for afflicted patients. Compared to other forms of incontinence, SUI cannot be easily treated with pharmacotherapy since it is inherently an anatomic problem. Treatment options include the use of bio-injectable materials to enhance closing pressures, and the placement of slings to bolster fascial support to the urethra. However, histologic findings of degeneration in the incontinent urethral sphincter invite the use of tissues engineering strategies to regenerate structures that aid in promoting continence. In this review, we will assess the role of stem cells in restoring multiple anatomic and physiological aspects of the sphincter. In particular, mesenchymal stem cells and CD34+ cells have shown great promise to differentiate into muscular and vascular components, respectively. Evidence supporting the use of cytokines and growth factors such as hypoxia-inducible factor 1-alpha, vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor and insulin-like growth factor further enhance the viability and direction of differentiation. Bridging the benefits of stem cells and growth factors involves the use of synthetic scaffolds like poly (1,8-octanediol-co-citrate) (POC) thin films. POC scaffolds are synthetic, elastomeric polymers that serve as substrates for cell growth, and upon degradation, release growth factors to the microenvironment in a controlled, predictable fashion. The combination of cellular, cytokine and scaffold elements aims to address the pathologic deficits to urinary incontinence, with a goal to improve patient symptoms and overall quality of life.
机译:作为一种单独的症状,压力性尿失禁(SUI)不会危及生命。然而,担心尿液意外泄漏会导致患病患者的生活质量参数显着下降。与其他形式的尿失禁相比,SUI很难通过药物治疗来治疗,因为它本质上是一个解剖学问题。治疗选择包括使用生物可注射材料增加闭合压力,以及放置吊索以增强筋膜对尿道的支撑。但是,尿失禁性括约肌变性的组织学发现促使组织工程策略的应用来再生有助于促进尿失禁的结构。在这篇综述中,我们将评估干细胞在恢复括约肌的解剖学和生理学方面的作用。特别是,间充质干细胞和CD34 + 细胞已显示出有望分化为肌肉和血管成分的巨大希望。支持使用细胞因子和生长因子(例如缺氧诱导因子1-alpha,血管内皮生长因子,碱性成纤维细胞生长因子,肝细胞生长因子和胰岛素样生长因子)的证据进一步增强了分化的活力和方向。桥接干细胞和生长因子的好处涉及使用合成支架,例如聚(1,8-辛二醇-柠檬酸酯)(POC)薄膜。 POC支架是合成的弹性体聚合物,可作为细胞生长的底物,降解后,可控,可预测的方式将生长因子释放到微环境中。细胞,细胞因子和支架元素的组合旨在解决尿失禁的病理缺陷,目的是改善患者症状和整体生活质量。

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