Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
Curr Opin Urol. 2024 Mar 1;34(2):44-51. doi: 10.1097/MOU.0000000000001149. Epub 2023 Nov 14.
This study aims to further understand the physiological mechanism of chondroitin sulfate treatment on the urinary bladder in cases of inflammation, by investigating the effect of chondroitin sulfate therapy on recovery of urothelial barrier in an in-vitro chronic injury model.
With inflammatory bladder conditions, the urothelial barrier seems decreased. Glycosaminoglycan (GAG) replacement therapy is supposed to help restore this barrier. Clinical studies on inflammatory bladder conditions are complicated because of the heterogeneous patient population, hence the need for preclinical models.
In a model using porcine urothelial cells, functional barrier (TEER) and barrier markers were assessed. Chronic urothelial damage was simulated through protamine sulfate instillations with and without subsequent chondroitin sulfate instillations during 3 days. Chondroitin sulfate instillations significantly improved TEER compared to protamine sulfate treatment only (TEER difference 310 Ω.cm 2 , P < 0.001). This consistent effect over 3 days resulted in a significant higher mean TEER value in the chondroitin sulfate treated group (difference 1855 Ω.cm 2 , P < 0.001). Enhanced recovery of chondroitin sulfate and other barrier markers was observed.Chondroitin sulfate therapy shows promise in facilitating the recovery of the urothelial barrier in cases of chronic damage. This preclinical study lends support to the use of clinical GAG replenishment therapy for patients with a chronically impaired urothelium.
本研究旨在通过研究硫酸软骨素治疗对体外慢性损伤模型中尿路上皮屏障恢复的影响，进一步了解硫酸软骨素治疗炎症性膀胱的生理机制。
在炎症性膀胱疾病中，尿路上皮屏障似乎减少了。糖胺聚糖 (GAG) 替代疗法被认为有助于恢复这种屏障。由于患者人群存在异质性，炎症性膀胱疾病的临床研究变得复杂，因此需要临床前模型。
在使用猪尿路上皮细胞的模型中，评估了功能性屏障 (TEER) 和屏障标志物。通过硫酸鱼精蛋白灌注模拟慢性尿路上皮损伤，并用和不用硫酸软骨素在 3 天内进行后续灌注。与硫酸鱼精蛋白处理相比，硫酸软骨素灌注显著提高了 TEER（TEER 差异 310 Ω·cm 2 ，P ＜0.001）。这种持续 3 天的一致效果导致硫酸软骨素处理组的平均 TEER 值显著升高（差异 1855 Ω·cm 2 ，P ＜0.001）。观察到硫酸软骨素和其他屏障标志物的恢复增强。硫酸软骨素治疗有望促进慢性损伤情况下尿路上皮屏障的恢复。这项临床前研究支持对慢性尿路上皮受损患者使用临床 GAG 补充治疗。
