Pezeshki Parmida Sadat, Mahboubi Amir, Mohammadi Ganjaroudi Negar, Ghalehtaki Reza, Majidi Zolbin Masoumeh, Salarvand Samaneh, Jolany Vangah Somayeh, Mehrjoo Asma, Kajbafzadeh Abdol-Mohammad
Pediatric Urology and Regenerative Medicine Research Center, Children's Medical Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Stem Cell Res Ther. 2025 Jul 18;16(1):387. doi: 10.1186/s13287-025-04503-2.
Radiation cystitis (RC) is a major complication of pelvic radiotherapy, leading to inflammation, vascular damage, and fibrosis. While mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) show promise in regenerative medicine, their therapeutic effects on RC remain unclear. This study evaluates the efficacy of human umbilical cord MSC-EVs (huMSC-EVs) in mitigating Radiation-induced bladder damage.
Animal models of RC were established using 20 Gy pelvic irradiation. Forty-four female Sprague-Dawley rats were divided into four groups: negative control (NC, no radiation), positive control (PC, radiation only), local treatment (LT, huMSC-EVs injected into the bladder wall), and systemic treatment (ST, intravenous huMSC-EVs). Bladder function and compliance were assessed via metabolic cage and urodynamic studies (UDS) at 6 and 24 weeks. Histopathological changes and inflammatory cytokine levels were evaluated at multiple time points.
Administration of huMSC-EVs significantly improved urinary frequency and hematuria. Histological analysis showed reduced urothelial disintegration and edema in the early phase, and improved urothelial integrity, reduced hyperplasia and vascular lesions, and restored bladder architecture in the late phase, in the treated groups. UDS demonstrated preserved bladder compliance and voiding efficiency in LT rats, with significantly higher voided volume (p < 0.01) and lower post-voiding residue (p < 0.05) compared to the PC group 24 weeks post-irradiation. Pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were markedly lowered and their levels were similar to the non-radiated NC group in LT-treated rats (p = 1.00, p = 0.22, p = 0.16), 24 weeks post-irradiation.
Local huMSC-EVs therapy effectively reduces RC-related bladder injury and preserves function, likely by modulating inflammatory response and epithelial regeneration. These findings highlight huMSC-EVs as a promising strategy to prevent chronic RC, warranting further clinical exploration.
放射性膀胱炎（RC）是盆腔放疗的主要并发症，可导致炎症、血管损伤和纤维化。虽然间充质干细胞衍生的细胞外囊泡（MSC-EVs）在再生医学中显示出前景，但其对RC的治疗效果仍不清楚。本研究评估人脐带MSC-EVs（huMSC-EVs）减轻放射性膀胱损伤的疗效。
采用20 Gy盆腔照射建立RC动物模型。44只雌性Sprague-Dawley大鼠分为四组：阴性对照组（NC，未照射）、阳性对照组（PC，仅照射）、局部治疗组（LT，将huMSC-EVs注入膀胱壁）和全身治疗组（ST，静脉注射huMSC-EVs）。在6周和24周时通过代谢笼和尿动力学研究（UDS）评估膀胱功能和顺应性。在多个时间点评估组织病理学变化和炎症细胞因子水平。
给予huMSC-EVs可显著改善尿频和血尿。组织学分析显示，治疗组在早期尿路上皮崩解和水肿减轻，晚期尿路上皮完整性改善、增生减少、血管病变减轻，膀胱结构恢复。UDS显示，LT组大鼠膀胱顺应性和排尿效率得以保留，与照射后24周的PC组相比，排尿量显著更高（p<0.01），残余尿量更低（p<0.05）。照射后24周，LT组大鼠促炎细胞因子TNF-α、IL-1β和IL-6明显降低，其水平与未照射的NC组相似（p=1.00，p=0.22，p=0.16）。
局部huMSC-EVs治疗可有效减轻与RC相关的膀胱损伤并保留功能，可能是通过调节炎症反应和上皮再生实现的。这些发现突出了huMSC-EVs作为预防慢性RC的一种有前景的策略，值得进一步临床探索。
