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Sci Rep. 2016 Aug 2;6:30881. doi: 10.1038/srep30881.

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

Kim A1, Yu HY1,2, Heo J2,3, Song M1, Shin JH1, Lim J2,3, Yoon SJ1,2, Kim Y2,3, Lee S2,3, Kim SW4, Oh W5, Choi SJ5, Shin DM2,3, Choo MS1.

Author information

1
Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
2
Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea.
3
Department of Physiology, University of Ulsan College of Medicine, Seoul, 05505, Korea.
4
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, Korea.
5
Biomedical Research Institute, MEDIPOST Co., Ltd., Seongnam-si, Gyeonggi-do, 13494, Korea.

Abstract

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.

PMID:
27481042
PMCID:
PMC4969614
DOI:
10.1038/srep30881
[Indexed for MEDLINE]
Free PMC Article

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