Laboratory for Experimental Urology, Organ Systems, Department of Development and Regeneration, University of Leuven, Leuven, Belgium.
The Institute of Urology, University College of London Hospital (UCLH), London, UK.
Nat Rev Urol. 2019 Feb;16(2):79-97. doi: 10.1038/s41585-018-0109-7.
Fibrosis is often caused by chronic tissue injury leading to a persisting inflammatory response with excessive accumulation of extracellular connective tissue proteins. Peyronie's disease, urethral stricture and penile (corpora cavernosa) fibrosis are localized fibrotic disorders of the penile connective tissues that can substantially impair a patient's quality of life. Research over the past few decades has revealed the ability of stem cells to secrete a wide range of paracrine factors, a characteristic that could be exploited therapeutically to prevent and treat several inflammatory and fibrotic diseases. In preclinical studies, mesenchymal stem cells (MSCs) have proven to be the most effective and readily available type of stem cells for therapeutic use. An important advantage of MSCs is their ability to circumvent the immune system and function as immunomodulatory 'drug stores' to influence multiple cell types simultaneously. Many studies using stem cells have been applied exclusively to corpora cavernosa fibrosis owing to its well-established disease models. A plethora of preclinical data suggest the benefit of stem cells for use in penile fibrosis. However, their exact mechanism of action and optimal timing and mode of administration must be determined before clinical translation.
纤维化通常由慢性组织损伤引起,导致持续的炎症反应,细胞外结缔组织蛋白过度积累。佩罗尼病、尿道狭窄和阴茎(海绵体)纤维化是阴茎结缔组织的局部纤维化疾病,会严重影响患者的生活质量。过去几十年来的研究揭示了干细胞分泌广泛的旁分泌因子的能力,这一特性可被用于治疗,以预防和治疗几种炎症和纤维化疾病。在临床前研究中,间充质干细胞 (MSCs) 已被证明是最有效和最容易获得的治疗用干细胞类型。MSCs 的一个重要优势是它们能够规避免疫系统,并作为免疫调节“药物库”,同时影响多种细胞类型。由于其完善的疾病模型,许多使用干细胞的研究都专门应用于海绵体纤维化。大量临床前数据表明干细胞对治疗阴茎纤维化有益。然而,在进行临床转化之前,必须确定其确切的作用机制以及最佳的给药时间和方式。