Tran Christine, Damaser Margot S
Glickman Urological and Kidney Institute, The Cleveland Clinic, USA.
The Cleveland Clinic, Department of Biomedical Engineering, 9500 Euclid Avenue ND20, Cleveland, OH 44195, USA.
Ther Adv Urol. 2015 Feb;7(1):22-40. doi: 10.1177/1756287214553968.
Voiding dysfunction encompasses a wide range of urologic disorders including stress urinary incontinence and overactive bladder that have a detrimental impact on the quality of life of millions of men and women worldwide. In recent years, we have greatly expanded our understanding of the pathophysiology of these clinical conditions. However, current gold standard therapies often provide symptomatic relief without targeting the underlying etiology of disease development. Recently, the use of stem cells to halt disease progression and reverse underlying pathology has emerged as a promising method to restore normal voiding function. Stem cells are classically thought to aid in tissue repair via their ability for multilineage differentiation and self-renewal. They may also exert a therapeutic effect via the secretion of bioactive factors that direct other stem and progenitor cells to the area of injury, and that also possess antiapoptotic, antiscarring, neovascularization, and immunomodulatory properties. Local injections of mesenchymal, muscle-derived, and adipose-derived stem cells have all yielded successful outcomes in animal models of mechanical, nerve, or external urethral sphincter injury in stress urinary incontinence. Similarly, direct injection of mesenchymal and adipose-derived stem cells into the bladder in animal models of bladder overactivity have demonstrated efficacy. Early clinical trials using stem cells for the treatment of stress urinary incontinence in both male and female patients have also achieved promising functional results with minimal adverse effects. Although many challenges remain to be addressed prior to the clinical implementation of this technology, novel stem-cell-based therapies are an exciting potential therapy for voiding dysfunction.
排尿功能障碍涵盖了广泛的泌尿系统疾病,包括压力性尿失禁和膀胱过度活动症,这些疾病对全球数百万男性和女性的生活质量产生了不利影响。近年来,我们对这些临床病症的病理生理学有了极大的扩展认识。然而,目前的金标准疗法通常只能缓解症状,而无法针对疾病发展的潜在病因。最近,使用干细胞来阻止疾病进展和逆转潜在病理已成为恢复正常排尿功能的一种有前景的方法。传统上认为干细胞通过其多谱系分化和自我更新的能力来辅助组织修复。它们还可能通过分泌生物活性因子发挥治疗作用,这些因子将其他干细胞和祖细胞引导至损伤区域,并且还具有抗凋亡、抗瘢痕形成、促进血管生成和免疫调节特性。在压力性尿失禁的机械性、神经性或尿道外括约肌损伤的动物模型中,局部注射间充质干细胞、肌肉来源的干细胞和脂肪来源的干细胞均取得了成功的结果。同样,在膀胱过度活动症的动物模型中,将间充质干细胞和脂肪来源的干细胞直接注入膀胱也已证明有效。早期使用干细胞治疗男性和女性压力性尿失禁的临床试验也取得了有前景的功能结果,且副作用最小。尽管在该技术临床应用之前仍有许多挑战需要解决,但新型基于干细胞的疗法是治疗排尿功能障碍的一种令人兴奋的潜在疗法。