Restoring the barrier of chronically damaged urothelium using chondroitin sulfate glycosaminoglycan-replenishment therapy.

Abstract

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.