Ji-Youn Chun

The Paracrine Effects of Mesenchymal Stem Cells Stimulate the Regeneration Capacity of Endogenous Stem Cells in the Repair of a Bladder-Outlet-Obstruction-Induced Overactive Bladder

Overactive bladder (OAB), which is characterized by the sudden and uncomfortable need to urinate with or without urinary leakage, is a challenging urological condition. The insufficient efficacy of current pharmacotherapies that uses antimuscarinic agents has increased the demand for novel long-term/stable therapeutic strategies. Here, we report the superior therapeutic efficacy of using mesenchymal stem cells (MSCs) for the treatment of OAB and a novel therapeutic mechanism that activates endogenous Oct4(+) primitive stem cells. We induced OAB using bladder-outlet-obstruction (BOO) in a rat model and either administered a single transplantation of human adipose-derived MSCs or daily intravenous injections of solifenacin, an antimuscarinic agent, for 2 weeks. Within 2 weeks, both the MSC- and solifenacin-treated groups similarly demonstrated relief from BOO-induced detrusor overactivity, hypertrophic smooth muscle, and neurological injuries. In contrast with the solifenacin-treated groups, a single transplantation of MSCs improved most OAB parameters to normal levels within 4 weeks. Although the transplanted human MSCs were hardly engrafted into the damaged bladders, the bladder tissues transplanted with MSCs increased rat sequence-specific transcription of Oct4, Sox2, and Stella, which are surrogate markers for primitive pluripotent stem cells. In addition, MSCs enhanced the expression of several genes, responsible for stem cell trafficking, including SDF-1/CXCR4, HGF/cMet, PDGF/PDGFR, and VEGF/VEGFR signaling axis. These changes in gene expression were not observed in the solifenacin-treated group. Therefore, we suggest the novel mechanisms for the paracrine effect of MSCs as unleashing/mobilizing primitive endogenous stem cells, which could not only explain the long-term/stable therapeutic efficacy of MSCs, but also provide promising new therapies for the treatment of OAB.

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.

Comparing Argus sling and artificial urinary sphincter in patients with moderate post-prostatectomy incontinence

Post-prostatectomy incontinence (PPI) is a main complication of radical prostatectomy. The purpose of this study was to compare the efficacy and safety of the Argus male sling (Argus) with that of artificial urinary sphincters (AUS) in patients with moderate PPI. A total of 33 moderate PPI patients underwent AUS or Argus implantation from January 2009 to June 2013 (13 AUS, 20 Argus). We defined moderate PPI as the use of 2–4 pads per day. To compare efficacy, we assessed the success rate between the two groups. Success was defined as the daily need for no pads or one small safety pad that remained dry most of the day. The mean patient age was 73.5±6.3 yr in the AUS group and 70.9±5.1 yr in the Argus group, and the mean follow-up period was 29.8±14.9 months in the AUS group and 24.7±11.8 months in the Argus group. The success rate was 72.7% in the AUS group and 85.0% in the Argus group (P=0.557). Abnormal postoperative pain persisted in more patients in the Argus group (6/20, 30%) than in the AUS group (1/13, 7.7%) (P=0.126). However, the rate of other complications was not different between the two groups (7.7% and 15.0% for AUS and Argus, respectively, P=0.822). Argus surgery showed similar success and complication rates to those of AUS in moderate PPI patients, indicating that it could be an alternative surgical option for the treatment of moderate PPI.

The fibrosis of ketamine, a noncompetitive N-methyl-d-aspartic acid receptor antagonist dose-dependent change in a ketamine-induced cystitis rat model

Abstract Ketamine abusers have greatly increased in number worldwide during recent years. The consumption of ketamine has increased, as have the number of published accounts of devastating urological sequelae. However, the mechanism of ketamine-associated urinary tract dysfunction remains unclear. This study was to evaluate the ketamine dose-dependency of ketamine-induced cystitis (KC) in a rat model. A total of 42 Sprague-Dawley rats (female, 10-week-old) were used. Each of the 7 KC rat models were induced by 1, 5, 10, 25 and 50 mg/kg ketamine intravenous injection for two weeks. For the sham group (n = 7), a phosphate-buffered saline (PBS) vehicle was used rather than ketamine hydrochloride. The cystometric parameters, histological examinations, staining for Masson’s trichome, cytokeratin, toluidine blue and quantitative PCR were measured at two weeks following the intervention. The voiding interval gradually decreased depending upon the ketamine dose of 1, 5, 10, 25, or 50 mg/kg, respectively, and was decreased compared with Sham. Bladder capacity was decreased as ketamine dose increased. In particular, the increase of fibrosis and submucosal apoptosis were found according to the increase of the ketamine dose. The bladder apoptosis in the KC rat model makes the fibrotic bladder change, and led us to hypothesize that fibrosis could contribute to the lower urinary-tract symptoms. We suggest that according to the pathophysiology evidence, fibrosis induced by apoptosis plays a key role in KC.

A Comparative Study of Outside-In and Inside-Out Transobturator Tape Procedures for Female Stress Urinary Incontinence: 7-Year Outcomes.

The aim of this study was to compare the long‐term surgical outcomes of the “inside‐out” (TVT‐O) and “outside‐in” (TOT) transobturator tape procedures for treating female stress urinary incontinence (SUI).

Clinical Factors Associated With Dose Escalation of Solifenacin for the Treatment of Overactive Bladder in Real Life Practice

Purpose To determine the baseline clinical characteristics associated with dose escalation of solifenacin in patients with overactive bladder (OAB). Methods We analyzed the data of patients with OAB (micturition frequency ≥8/day and urgency ≥1/day) who were treated with solifenacin and followed up for 24 weeks. According to our department protocol, all the patients kept voiding diaries, and OAB symptom scores (OABSS) were monitored at baseline and after 4, 12, and 24 weeks of solifenacin treatment. Results In total, 68 patients (mean age, 60.8±10.0 years) were recruited. The dose escalation rate by the end of the study was 41.2%, from 23.5% at 4 weeks and 17.6% at 12 weeks. At baseline, the dose escalator group had significantly more OAB wet patients (53.6% vs. 20.0%) and higher total OABSS (10.2±2.4 vs. 7.9±3.5, P=0.032) than the nonescalator group. OAB wet (odds ratio [OR], 4.615; 95% confidence interval [CI], 1.578-13.499; P<0.05) and total OABSS (OR, 1.398; 95% CI, 1.046-1.869; P<0.05) were found to be independently associated with dose escalation. Conclusions Patients who have urgency urinary incontinence and high total OABSS have a tendency for dose escalation of solifenacin.

Correlation of the Overactive Bladder Symptom Score, and the Voiding Diary and Urodynamic Parameters in Patients with Overactive Bladder Syndrome

To investigate correlations between the overactive bladder symptom score (OABSS), the voiding diary, and urodynamic parameters in women with overactive bladder syndrome (OAB).

Cooling characteristic of field emission from metals and semiconductors

We have theoretically investigated the cooling effect of field emission from metals and n-type semiconductors. The potential energy was found as a function of the tip curvature and the emission distance. The use of the obtained potential leads to the calculation of the energy exchange as a function of two geometrical quantities. The cooling power needed for micro-electronic device is obtained for field emission from the highly n-doped Si semiconductor.