Treatment of interstitial cystitis with intravesical instillation of recombinant human collagen type Ⅲ

Interstitial cystitis (IC) is a chronic condition characterized by frequent urination, urgency, and pelvic pain. While its pathogenesis remains incompletely understood, the prevailing epithelial theory suggests that a defective glycosaminoglycan (GAG) layer increases bladder permeability, allowing urinary toxins to chronically stimulate the detrusor muscle and activate mast cells. Current therapies, such as intravesical hyaluronic acid instillation, have demonstrated limited efficacy. This study aimed to evaluate the feasibility of sterile recombinant human collagen type III (rHCIII) in mitigating bladder injury and its histological effects on urothelial integrity.

An IC rat model was established using protamine sulfate and lipopolysaccharide. The model was subsequently treated with sterile rHCⅢ via bladder instillation. Bladder tissues were analyzed using Hematoxylin-eosin (H&E) staining for general histopathology, Masson and van Gieson staining for collagen fiber organization, and Toluidine blue (TB) staining for mast cell infiltration. Apoptosis was assessed by Terminal Deoxynucleotidyl Transferase mediated dUTP Nick-End Labeling (TUNEL) staining and immunohistochemistry for Caspase-3. The localization of the perfused rHCⅢ was tracked using immunohistochemistry for a 6×Histidine (HIS) tag.

Immunohistochemistry confirmed the presence of rHCⅢ in the bladder mucosal and submucosal layers. Treatment with rHCⅢ significantly reduced bladder cell apoptosis compared to the IC group (p < 0.001). Furthermore, the collagen fibers in the submucosal and muscular layers demonstrated a more compact and organized arrangement post-treatment. Mast cell infiltration was also markedly diminished following rHCⅢ instillation (p < 0.001).

Intravesical instillation of sterile rHCⅢ mitigates apoptosis of mucosal epithelial cells and reinforces the submucosal collagen structure. This intervention promotes a more organized tissue architecture, which may help maintain urothelial structural integrity. These findings provide preclinical evidence supporting the repair-oriented potential of rHCⅢ instillation for interstitial cystitis.