Mesenchymal Stem Cell Therapy Alleviates Interstitial Cystitis by Activating Wnt Signaling Pathway.
Interstitial cystitis (IC) is a syndrome characterized by urinary urgency, frequency, pelvic pain, and nocturia in the absence of bacterial infection or identifiable pathology. IC is a devastating disease that certainly decreases quality of life. However, the causes of IC remain unknown and no effective treatments or cures have been developed. This study evaluated the therapeutic potency of using human umbilical cord-blood-derived mesenchymal stem cells (UCB-MSCs) to treat IC in a rat model and to investigate its responsible molecular mechanism. IC was induced in 10-week-old female Sprague-Dawley rats via the instillation of 0.1 M HCl or phosphate-buffered saline (PBS; sham). After 1 week, human UCB-MSC (IC+MSC) or PBS (IC) was directly injected into the submucosal layer of the bladder. A single injection of human UCB-MSCs significantly attenuated the irregular and decreased voiding interval in the IC group. Accordingly, denudation of the epithelium and increased inflammatory responses, mast cell infiltration, neurofilament production, and angiogenesis observed in the IC bladders were prevented in the IC+MSC group. The injected UCB-MSCs successfully engrafted to the stromal and epithelial tissues and activated Wnt signaling cascade. Interference with Wnt and epidermal growth factor receptor activity by small molecules abrogated the benefits of MSC therapy. This is the first report that provides an experimental evidence of the therapeutic effects and molecular mechanisms of MSC therapy to IC using an orthodox rat animal model. Our findings not only provide the basis for clinical trials of MSC therapy to IC but also advance our understanding of IC pathophysiology.
1 Department of Urology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Miho
M
Song
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.|3 Department of Biomedical Sciences, Seoul National University College of Medicine , Seoul, Korea.
Jisun
J
Lim
1 Department of Urology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.|2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Hwan Yeul
HY
Yu
1 Department of Urology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Junsoo
J
Park
1 Department of Urology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Ji-Youn
JY
Chun
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.|4 Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Jaeho
J
Jeong
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.|4 Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Jinbeom
J
Heo
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.|4 Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Hyunsook
H
Kang
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.|4 Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
YongHwan
Y
Kim
5 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Yong Mee
YM
Cho
6 Department of Biochemistry and Molecular Biology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Seong Who
SW
Kim
7 Biomedical Research Institute, MEDIPOST Co., Ltd. , Seoul, Korea.
Wonil
W
Oh
7 Biomedical Research Institute, MEDIPOST Co., Ltd. , Seoul, Korea.
Soo Jin
SJ
Choi
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Sung-Wuk
SW
Jang
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Sanghyeok
S
Park
2 Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.|4 Department of Physiology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Dong-Myung
DM
Shin
1 Department of Urology, Asan Medical Center, University of Ulsan College of Medicine , Seoul, Korea.
Myung-Soo
MS
Choo
D000818:Animals; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000628:therapy*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000503:physiopathology; D014554:Urination / Q000502:physiology; D014555:Urination Disorders / Q000628:therapy*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*
D051153:Wnt Proteins; D004815:Epidermal Growth Factor