Bladder wall injection of mesenchymal stem cells ameliorates bladder inflammation,overactivity, and nociception in a chemically induced interstitial cystitis-like rat model

Introduction and hypothesis

We investigated the effects of bladder wall injection of mesenchymal stem cells (MSCs) on bladder tissues, function, and nociceptive behavior in a chemically induced interstitial cystitis-like rat model.

Methods

Chemical cystitis of female rats was induced by intravesical instillation of 0.1 N hydrochloride (HCl) once a week for 2 weeks. Bladders were harvested 1, 2, 3, and 4 weeks after the second application for histological examination. Adipose-derived MSCs (HCl?+?MSCs) or phosphate-buffered saline (HCl?+?PBS) was injected into the bladder wall at the time of the second application of HCl. Histological examination, nociceptive behavior, and cystometrograms were evaluated 2 weeks after the injection compared with controls, which received instillation and injection of PBS into the bladder (sham + PBS).

Results

The number of mast cells and expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) were significantly increased at 1 and 2 weeks, and expression of collagen fibers was significantly increased from 2–4 weeks after the second application of HCl. Significantly increased nociceptive behavior, number of mast cells, expression of TNF-α, TGF-β, and collagen fibers were observed in HCl?+?PBS compared with sham?+?PBS, whereas these changes were significantly decreased in HCl?+?MSCs compared with HCl?+?PBS. In addition, bladder capacity and voiding threshold pressures were significantly decreased in HCl?+?PBS but not in HCl?+?MSCs compared with sham?+?PBS.

Conclusions

The results suggest that bladder injection of MSCs ameliorates inflammation and fibrosis in bladder tissues, bladder overactivity, and nociception in a rat model of chemically induced cystitis.