Introduction
Interstitial cystitis/bladder pain syndrome (IC/BPS) arises from multiple etiologic factors, and most studies suggest that stem cell therapy is beneficial. Although stem cells support bladder tissue regeneration, their effects on neuroinflammation and central pain pathways remain unclear. This study aimed to investigate how human umbilical cord–derived mesenchymal stem cells (HU-MSCs) delivered to the bladder wall influence neuroinflammatory mechanisms contributing to chronic pain in an LPS/PS-induced IC/BPS rat model.

Material and method
IC/BPS was induced in rats using lipopolysaccharide/protamine sulfate (LPS/PS) with 750 µg LPS and 10 mg PS administered weekly for 5 weeks via intravesical instillation. HU-MSCs were expanded to passage 3, and 1.2 × 106 cells in 0.2 ml PBS were injected into the bladder dome one week after LPS/PS treatment. Rats were euthanized one week later, and bladder and spinal cord tissues were paraffin-embedded. Bladder inflammation scores were assessed with H&E staining, while mast cell count and distribution were evaluated with toluidine blue. Neuroinflammation markers (Iba-1 and TNF-α) in spinal cord sections were analyzed by immunohistochemistry.

Results
The LPS/PS group showed elevated bladder inflammation scores, increased mast cell infiltration, and higher anti-TNF-α and anti-IBA-1 levels compared with controls. HU-MSC treatment improved chronic inflammatory changes, reducing inflammation scores and mast cell infiltration. Immunohistochemistry demonstrated decreased spinal cord anti-TNF-α and anti-IBA-1 expression following HU-MSC administration.

Conclusion
HU-MSCs exhibit therapeutic potential for IC/BPS by promoting bladder regeneration, reducing inflammation and mast cell activity, and attenuating spinal neuroinflammation.

Brief summary
Intravesical hUC-MSC therapy reduced bladder inflammation, mast cell infiltration, and spinal dorsal horn neuroinflammation in IC/BPS rats, demonstrating both peripheral and central therapeutic benefits.