Abstract
Background and Purpose Bladder pain syndrome/interstitial
cystitis (BPS/IC) has been clinically treated with glycosaminoglycan
(GAG) replenishment therapy. [1, 2] This study was designed to
further understand the physiological mechanism behind chondroitin
sulfate (CS) treatment and to determine the effect of CS-therapy on
recovery of urothelial barrier in an in-vitro chronic injury
model.Experimental Approach In differentiated porcine urothelial
cells the functional barrier was measured by transepithelial electrical
resistance (TEER). A chronic urothelium was inflicted by multiple
protamine instillations (3/day for 3 days), to approximate BPS/IC
urothelium conditions. CS was instilled afterwards. Recovery of barrier
function was followed in time. Additional analyses were performed for
immunohistochemistry for barrier markers (tight junctions, GAG’s,
umbrella cells) and scanning electron microscopy. Statistics were
described by means ± standard error, α = 0.05.Key Results Barrier recovery (TEER) improved significantly with
CS instillations compared to protamine only (T=7, 899.1
[Ω.cm2] versus 589.6
[Ω.cm2], p<0.001, 95% CI -394;-255).
This recovery effect was seen on all three days and resulted in a
significantly higher average TEER value in the CS group after 3 days
(2606 Ω.cm2 vs 750.5 Ω.cm2).
Immunohistochemistry and scanning electron microscopy showed decreased
barrier markers after protamine treatment and enhanced recovery of
urothelial GAG’s and other barrier markers after therapeutic
instillations.Conclusion and Implications GAG replenishment with CS can
improve recovery of barrier function of chronically damaged urotheliumin-vitro . This preclinical study supports the hypothesis behind
the use of clinical GAG replenishment therapy for patients with a
chronically impaired urothelium.
Key words: Bladder pain syndrome / Interstitial cystitis,
GAG-therapy, In-vitro study