Open AccessMesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder
Author(s) -
Aram Kim,
Hwan Yeul Yu,
Jinbeom Heo,
MinKyu Song,
Ji Sun Shin,
Jisun Lim,
Soo-Jung Yoon,
YongHwan Kim,
Seungun Lee,
Seong Who Kim,
Wonil Oh,
Soo Jin Choi,
DongMyung Shin,
MyungSoo Choo
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep30881
Subject(s) - mesenchymal stem cell , medicine , fibrosis , urinary bladder , interstitial cystitis , cancer research , pathophysiology , downregulation and upregulation , ketamine , urinary system , pharmacology , pathology , biology , gene , anesthesia , biochemistry
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.