Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder

نویسندگان

  • Aram Kim
  • Hwan Yeul Yu
  • Jinbeom Heo
  • Miho Song
  • Jung-Hyun Shin
  • Jisun Lim
  • Soo-Jung Yoon
  • YongHwan Kim
  • Seungun Lee
  • Seong Who Kim
  • Wonil Oh
  • Soo Jin Choi
  • Dong-Myung Shin
  • Myung-Soo Choo
چکیده

Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-β signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1 × 10(6)) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2016