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

Int Urogynecol J. 2018 Nov;29(11):1615-1622. doi: 10.1007/s00192-018-3592-8. Epub 2018 Mar 6.

Abstract

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.

Keywords: Adipose; Hydrochloride; Interstitial cystitis; Mesenchymal stem cells; Rats.

MeSH terms

  • Administration, Intravesical
  • Animals
  • Cystitis, Interstitial / chemically induced
  • Cystitis, Interstitial / physiopathology
  • Cystitis, Interstitial / therapy*
  • Disease Models, Animal
  • Female
  • Fibrosis
  • Inflammation
  • Injections
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells*
  • Nociception / physiology*
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism
  • Urinary Bladder / pathology*
  • Urinary Bladder / physiopathology

Substances

  • Tumor Necrosis Factor-alpha