The Efficacy and Safety of a Human Perirenal Adipose TissueDerived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model

BACKGROUND@#Interstitial cystitis (IC) is a chronic and intractable disease that can severely deteriorate patients’ quality of life. Recently, stem cell therapy has been introduced as a promising alternative treatment for IC in animal models. We aimed to verify the efficacy and safety of the human perirenal adipose tissue-derived stromal vascular fraction (SVF) in an IC rat model. @*METHODS@#From eight-week-old female rats, an IC rat model was established by subcutaneous injection of 200 lg of uroplakin3A. The SVF was injected into the bladder submucosal layer of IC rats, and pain scale analysis, awakening cytometry, and histological and gene analyses of the bladder were performed. For the in vivo safety analysis, genomic DNA purification and histological analysis were also performed to check tumorigenicity and thrombus formation. @*RESULTS@#The mean pain scores in the SVF 20 ll group were significantly lower on days 7 and 14 than those in the control group, and bladder intercontraction intervals were significantly improved in the SVF groups in a dose-dependent manner. Regeneration of the bladder epithelium, basement membrane, and lamina propria was observed in the SVF group.In the SVF groups, however, bladder fibrosis and the expression of inflammatory markers were not significantly improved compared to those in the control group. @*CONCLUSION@#This study demonstrated that a perirenal adipose tissue-derived SVF is a promising alternative for the management of IC in terms of improving bladder pain and overactivity.

A Multicenter, Open-Label, Observational Study Evaluating the Quality of Life After Using a Hydrophilic-Coated Catheter (SpeediCath) With Self-Intermittent Catheterization / 대한배뇨장애요실금학회지

Purpose@#We evaluated the change in patient quality of life after the use of a hydrophilic-coated catheter (SpeediCath) in adults requiring intermittent catheterization (IC). @*Methods@#This was a multicenter, open-label, observational study using the Patient Perception of Intermittent Catheterization (PPIC) questionnaire and the Intermittent Self-Catheterization questionnaire (ISC-Q) and safety at 12 and 24 weeks in adult patients who had already used other type of catheters prior to switching to SpeediCath or in patients undergoing self-IC for the first time for any reason. @*Results@#Among a total of 360 subjects, 215 (59.7%) were women, and the mean age was 62.0±13.2 years. At 24 weeks, the satisfaction rate after using SpeediCath was 84.1%, and 80% of patients responded that they could easily perform IC. In total, 81.6% of patients were willing to continue using SpeediCath. The mean ISC-Q score was 54.90±18.65 at 24 weeks. Men found less interference in their daily life by performing IC than women and found it easier to handle the catheter before it was inserted into the urethra. At week 12, the mean change in ISC-Q was significantly greater in patients <65 years (20.24±23.55) than in those ≥65 years (7.57±27.70, P=0.049), but there was no difference at 24 weeks. The most common adverse events were urinary tract infection in 9.72%, gross hematuria in 2.78%, and urethral pain in 1.39%. @*Conclusions@#The use of a SpeediCath provided good quality of life for patients who needed self-IC regardless of age or sex.

Elderly kidney transplant recipients have favorable outcomes but increased infection-related mortality

The number of elderly patients with end-stage kidney disease has been increasing, but the outcomes of kidney transplants (KT) remain poorly understood in elderly patients. Therefore, we evaluated the clinical outcomes of elderly KT recipients and analyzed the impact of elderly donors. Methods: This retrospective cohort study included patients who underwent KT between 2000 and 2019. KT recipients were divided into four groups according to a combination of recipient and donor age (≥60 or <60 years); elderly recipients: old-to-old (n = 46) and young-to-old (n = 83); young recipients: old-to-young (n = 98) and young-to-young (n = 796). We compared the risks of mortality, graft failure, and acute rejection between groups using Cox regression analysis. Results: The incidence of delayed graft function, graft failure, and acute rejection was not different among groups. Annual mean tacrolimus trough level was not lower in elderly recipients than young recipients during 10-year follow-up. Mortality was significantly higher in elderly recipients (p = 0.001), particularly infection-related mortality (p < 0.001). In multivariable Cox regression analysis, old-toold and young-to-old groups had increased risk of mortality (adjusted hazard ratio [aHR], 2.89; 95% confidence interval [CI], 1.14– 7.32; p = 0.03; aHR, 3.06; 95% CI, 1.51–6.20; p = 0.002). However, graft failure and acute rejection risks were not increased in elderly recipients. Conclusion: In elderly recipients, graft survival and acute rejection-free survival were not inferior to those of young recipients. However, mortality, especially risk of infection-related death, was increased in elderly recipients. Thus, low immunosuppression intensity might help decrease mortality in elderly recipients.

Predictive Factors of De Novo Overactive Bladder After Radical Prostatectomy in Patients With Clinically Localized Prostate Cancer: A Prospective Observational Study

Purpose@#To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). @*Materials and Methods@#We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. @*Results@#Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. @*Conclusions@#de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.

Predictive Factors of De Novo Overactive Bladder After Radical Prostatectomy in Patients With Clinically Localized Prostate Cancer: A Prospective Observational Study

Purpose@#To evaluate the incidence of de novo overactive bladder (OAB) and the factors related to its occurrence following radical prostatectomy (RP) in patients with clinically localized prostate cancer (PCa). @*Materials and Methods@#We prospectively examined 50 patients without OAB who underwent RP for clinically localized PCa in our institution from August 2019 to February 2020. We performed assessments using the International Prostate Symptom Score (IPSS), the Overactive Bladder Symptom Score (OABSS), and uroflowmetry before surgery and 3 months after RP. OAB was defined as a score of 1 or more on the urgency components of the OABSS. Three months after RP, the patients were divided into 2 groups based on the presence of de novo OAB symptoms. We evaluated the patients’ demographics and outcomes after RP according to their de novo OAB grouping. The predictive factors of de novo OAB after RP were analyzed using a multivariate logistic regression model. @*Results@#Of the 50 patients, 22 (44%) had de novo OAB 3 months after RP. The patients in the de novo OAB group were older, had higher preoperative IPSS storage subscores, and had larger volumes of postvoid residual urine on preoperative uroflowmetry than those in the non-de novo OAB group. Multivariate analysis showed that age and preoperative IPSS storage subscores were predictive factors of de novo OAB after RP. @*Conclusions@#de novo OAB was observed in 44% of the patients 3 months after RP. Age and preoperative IPSS storage subscores were predictive factors of de novo OAB following RP.

Serum Testosterone Level Can Be Predictive Factor for Upstaging in Clinically Localized Prostate Cancer

Purpose@#To determine an appropriate surgical technique, it is important to predict pathological results for patientswith clinically localized prostate cancer (PCa) eligible for nerve-sparing radical prostatectomy (NSRP). Severalstudies have highlighted that serum testosterone level was associated with aggressive features of PCa. Therefore,we analyzed factors, including serum testosterone, to predict upstaging and upgrading after surgery for patientswith clinically localized PCa eligible for NSRP. @*Materials and Methods@#We retrospectively evaluated patients who underwent radical prostatectomy (RP) betweenJanuary 2015 and May 2018 at our institution. Patients with Gleason grade group 1 or 2 on biopsy,prostate-specific antigen<10, and ≤clinical/radiologic stage T2 were included in this study. Upstaging andupgrading were defined as pathological stage≥T3a and Gleason grade group≥3, respectively. We evaluatedthe patients’ demographics and outcomes according to upstaging and upgrading after surgery. Predictive factorsfor upstaging and upgrading were analyzed using a multivariate logistic regression model. @*Results@#Of 108 patients included in the study, upstaging and upgrading after surgery were observed in 24 (22.2%)and 36 (33.3%), respectively. Low serum testosterone level, small prostate size, and positive core number≥3on biopsy were identified as predictive factors for upstaging in multivariate analysis. Although serum testosteronewas associated with upgrading in univariate analysis, only clinical/radiologic stage and biopsy Gleason grade groupwere observed as predictive factors for upgrading in multivariate analysis. @*Conclusions@#Serum testosterone level was identified as a predictive factor for upstaging after RP for clinicallylocalized PCa eligible for NSRP.

Impact of Multiple Prostate Biopsies: Risk of Perioperative Complications and Biochemical Recurrence After Radical Prostatectomy

Purpose@#The aim of this study was to analyze the perioperative complications and oncological outcomes of radical prostatectomy (RP) in patients who underwent multiple prostate biopsies. @*Materials and Methods@#A total of 1,112 patients who underwent RP between January 2009 and April 2016 at 4 different centers were included in this study. We divided these patients into 2 groups: patients who underwent only 1st biopsy, and those who underwent 2nd or more repeated biopsies. The association between the number of prior biopsies and perioperative complications and biochemical recurrence (BCR) was analyzed. @*Results@#Of 1,112 patients, 1,046 patients (94.1%) underwent only 1st biopsy, and 66 (5.9%) underwent 2nd or more repeated biopsies. There were no significant differences in preoperative prostate-specific antigen levels, operation times, blood loss volumes, or hospital stay durations (all p＞0.05). Patients who underwent multiple prostate biopsies presented with a localized tumor significantly more often (p＜0.05). The Gleason score and rate of positive surgical margins were significantly lower in patients with multiple biopsies (all p＜0.05). The Cox proportional hazards model analysis indicated that there was no association between the number of prior prostate biopsies and BCR (p＞0.05). Kaplan-Meier curve analysis indicated that BCR-free survival rates between the 2 groups were similar (p＞0.05). @*Conclusions@#Multiple prostate biopsies are not associated with an increased risk of perioperative complications, adverse pathological outcomes, or higher rates of BCR in patients who have undergone RP. (Korean J Urol Oncol 2020;18:24-31)

Efficacy of Androgen Deprivation Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Docetaxel-Based Chemotherapy

PURPOSE: The purpose of this study was to determine the comparative effectiveness of androgen deprivation therapy (ADT) combined with docetaxel (DTX)-based chemotherapy in Korean and Japanese castration-resistant prostate cancer (CRPC) patient cohorts.MATERIALS AND METHODS: Metastatic CRPC patients who underwent more than three DTX-based chemotherapy cycles in Korea and Japan between 2002 and 2017 were retrospectively analyzed and divided into the DTX-only (DTX, n=30) and combination (DTX+ADT, n=46) groups. Progression-free survival (PFS) was calculated as the time from the start of chemotherapy to the occurrence of either disease progression (prostate-specific antigen [PSA] progression or radiographic progression) or death. The primary end point was PFS and the secondary end point was overall survival (OS).RESULTS: In the DTX and DTX+ADT groups, the median PFS was 6.0 and 11.0 months (log-rank p=0.053). The multivariate Cox regression analysis revealed that the significant predicting factors of PFS were ADT administration (hazard ratio [HR], 0.478; 95% confidence interval [CI], 0.284–0.804; p=0.005) and number of DTX-based chemotherapy cycles (HR, 0.934; 95% CI, 0.899–0.970; p<0.001). In the DTX and DTX+ADT groups, the median OS was 16.0 and 19.5 months (log-rank p=0.825). Through multiple Cox regression analysis, we found that the significant predicting factors of OS were the PSA nadir level (HR, 1.001; 95% CI, 1.000–1.002; p<0.001) and number of DTX-based chemotherapy cycles (HR, 0.932; 95% CI, 0.876–0.991; p=0.024).CONCLUSIONS: Concurrent DTX-based chemotherapy and ADT may be beneficial compared with DTX-based chemotherapy alone in chemotherapy-naïve metastatic CRPC patients in terms of the PFS, but not the OS.

Artificial Urinary Sphincter for Postradical Prostatectomy Urinary Incontinence — Is It the Best Option? / 대한배뇨장애요실금학회지

Male stress urinary incontinence (SUI) can undoubtedly reduce quality of life and promote personal distress and psychosocial alienation. The frequency of postprostatectomy urinary incontinence (PPI) counts on the characterization of urinary incontinence and the periods of patient follow-up. Operational therapeutics, for instance, urethral male slings and artificial urinary sphincters, are well-chosen as adequate and secure surgeries for male SUI in men with continual PPI when conservative treatment is ineffective. Over the former 2 decades, surgery has progressed regarding both operative approach and sling architecture. However, there are no guidelines about when surgery should be carried out and which is the most appropriate surgical option. In this review, we summarize recent advances in implantable devices for PPI and also discuss traditional surgical care. When we are planning the male PPI surgery, careful preoperative work-up should be performed and surgical method should be chosen according to the severity of the disease. Male sling is preferred in mild and moderate symptomatic patients with normal detrusor pressure and it is recommended to select traditional artificial urinary sphincter device in those with severe symptoms. It is expected that effective devices without adverse events will be developed with technical advances in near future.

Susceptibility of the Index Urinary Tract Infection to Prophylactic Antibiotics Is a Predictive Factor of Breakthrough Urinary Tract Infection in Children with Primary Vesicoureteral Reflux Receiving Continuous Antibiotic Prophylaxis

BACKGROUND: Few studies have reported on breakthrough urinary tract infection (UTI) associated with the susceptibility of index UTI to prophylactic antibiotics in children with primary vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). We assessed the impact of the susceptibility of index UTI to prophylactic antibiotics in breakthrough UTIs in children with primary VUR receiving CAP. METHODS: We retrospectively reviewed the medical records of 81 children with primary VUR who were diagnosed after febrile or symptomatic UTI and subsequently received trimethoprim-sulfamethoxazole (TMP-SMX) as CAP between January 2010 and December 2013. We allocated children to a susceptible group or a resistant group based on the susceptibility of index UTI to TMP-SMX. We evaluated patient demographics and clinical outcomes after CAP according to the susceptibility of index UTI to TMP-SMX. Multivariate analysis was used to identify the predictive factors for breakthrough UTI. RESULTS: Of the 81 children, 42 were classified into the susceptible group and 39 into the resistant group. The proportion of breakthrough UTI was 31.0% (13/42) in the susceptible group and 53.8% (21/39) in the resistant group (P = 0.037). Progression of renal scarring was observed in 0% of children in the susceptible group and 15% in the resistant group (P = 0.053). Multivariate analysis showed that TMP-SMX resistance and initial renal scarring were significant predictors of breakthrough UTI. CONCLUSION: Susceptibility of index UTI to prophylactic antibiotics is a risk factor of breakthrough UTI and is associated with poor clinical outcomes in children with primary VUR receiving CAP.

In Vivo Safety and Regeneration of Long-Term Transported Amniotic Fluid Stem Cells for Renal Regeneration

BACKGROUND: Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo. METHODS: For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery. RESULTS: The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of proinflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells. CONCLUSION: This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.

In Vivo Validation Model of a Novel Anti-Inflammatory Scaffold in Interleukin-10 Knockout Mouse

BACKGROUND: We fabricated anti-inflammatory scaffold using Mg(OH)2-incorporated polylactic acid-polyglycolic acid copolymer (MH-PLGA). To demonstrate the anti-inflammatory effects of the MH-PLGA scaffold, an animal model should be sensitive to inflammatory responses. The interleukin-10 knockout (IL-10 KO) mouse is a widely used bowel disease model for evaluating inflammatory responses, however, few studies have evaluated this mouse for the anti-inflammatory scaffold. METHODS: To compare the sensitivity of the inflammatory reaction, the PLGA scaffold was implanted into IL-10 KO and C57BL/6 mouse kidneys. Morphology, histology, immunohistochemistry, and gene expression analyses were carried out at weeks 1, 4, 8, and 12. The anti-inflammatory effect and renal regeneration potency of the MH-PLGA scaffold was also compared to those of PLGA in IL-10 KO mice. RESULTS: The PLGA scaffold-implanted IL-10 KO mice showed kidneys relatively shrunken by fibrosis, significantly increased inflammatory cell infiltration, high levels of acidic debris residue, more frequent CD8-, C-reactive protein-, and ectodysplasin A-positive cells, and higher expression of pro-inflammatory and fibrotic factors compared to the control group. The MH-PLGA scaffold group showed lower expression of pro-inflammatory and fibrotic factors, low immune cell infiltration, and significantly higher expression of anti-inflammatory factors and renal differentiation related genes compared to the PLGA scaffold group. CONCLUSION: These results indicate that the MH-PLGA scaffold had anti-inflammatory effects and high renal regeneration potency. Therefore, IL-10 KO mice are a suitable animal model for in vivo validation of novel anti-inflammatory scaffolds.

A Novel Dorsal Slit Approached Non-Ischemic Partial Nephrectomy Method for a Renal Tissue Regeneration in a Mouse Model

BACKGROUND: Kidney ischemia-reperfusion (IR) via laparotomy is a conventional method for kidney surgery in a mouse model. However, IR, an invasive procedure, can cause serious acute and chronic complications through apoptotic and inflammatory pathways. To avoid these adverse responses, a Non-IR and dorsal slit approach was designed for kidney surgery. METHODS: Animals were divided into three groups, 1) sham-operated control; 2) IR, Kidney IR via laparotomy; and 3) Non-IR, Non-IR and dorsal slit. The effects of Non-IR method on renal surgery outcomes were verified with respect to animal viability, renal function, apoptosis, inflammation, fibrosis, renal regeneration, and systemic response using histology, immunohistochemistry, real-time polymerase chain reaction, serum chemistry, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and Masson's trichrome staining. RESULTS: The Non-IR group showed 100% viability with mild elevation of serum blood urea nitrogen and creatinine values at day 1 after surgery, whereas the IR group showed 20% viability and lethal functional abnormality. Histologically, renal tubule epithelial cell injury was evident on day 1 in the IR group, and cellular apoptosis enhanced TUNEL-positive cell number and Fas/caspase-3 and KIM-1/NGAL expression. Inflammation and fibrosis were high in the IR group, with enhanced CD4/CD8-positive T cell infiltration, inflammatory cytokine secretion, and Masson's trichrome stain-positive cell numbers. The Non-IR group showed a suitable microenvironment for renal regeneration with enhanced host cell migration, reduced immune cell influx, and increased expression of renal differentiation-related genes and anti-inflammatory cytokines. The local renal IR influenced distal organ apoptosis and inflammation by releasing circulating pro-inflammatory cytokines. CONCLUSION: The Non-IR and dorsal slit method for kidney surgery in a mouse model can be an alternative surgical approach for researchers without adverse reactions such as apoptosis, inflammation, fibrosis, functional impairment, and systemic reactions.

Optimal Stem Cell Transporting Conditions to Maintain Cell Viability and Characteristics

BACKGROUND: The preservation of stem cell viability and characteristics during cell transport from the bench to patients can significantly affect the success of cell therapy. Factors such as suspending medium, time, temperature, cell density, and container type could be considered for transport conditions. METHODS: To establish optimal conditions, human amniotic fluid stem cells' (AFSCs) viabilities were analyzed under different media {DMEM(H), DMEM/F-12, K-SFM, RPMI 1640, α-MEM, DMEM(L), PBS or saline}, temperature (4, 22 or 37 ℃), cell density (1 × 10⁷ cells were suspended in 0.1, 0.5, 1.0 or 2.0 mL of medium) and container type (plastic syringe or glass bottle). After establishing the transport conditions, stem cell characteristics of AFSCs were compared to freshly prepared cells. RESULTS: Cells transported in DMEM(H) showed relatively higher viability than other media. The optimized transport temperature was 4 ℃, and available transport time was within 12 h. A lower cell density was associated with a better survival rate, and a syringe was selected as a transport container because of its clinical convenience. In compare of stem cell characteristics, the transported cells with established conditions showed similar potency as the freshly prepared cells. CONCLUSION: Our findings can provide a foundation to optimization of conditions for stem cell transport.

A Higher Ratio of Serum Calcium to Magnesium Is Associated With Aggressive Clinicopathological Characteristics in the Patients Who Underwent Radical Prostatectomy

PURPOSE: Changes in magnesium (Mg) concentration and calcium-to-magnesium ratio (Ca/Mg) play a critical role in cancer cell proliferation. In this study, we evaluated the association between preoperative Ca/Mg ratio and clinicopathological characteristics of prostate cancer. MATERIALS AND METHODS: Preoperative serum levels of Ca and Mg, as well as the Ca/Mg ratio, were retrospectively analyzed in 319 consecutive patients with prostate cancer who underwent radical prostatectomy at our institution between February 2014 and June 2016. Blood Ca and Mg levels, together with the Ca/Mg ratio, were analyzed in relation to the patients' demographic and clinicopathological characteristics. RESULTS: Preoperative Ca/Mg ratio was significantly higher in patients with pathologic Gleason score (pGS)≥8 than in those with pGS≤7 (mean [95% confidence interval]: 4.45 [4.35–4.56] vs. 4.32 [4.27–4.38], p=0.037). The Ca/Mg ratio was positively correlated with preoperative prostate-specific antigen (PSA) levels (r=0.116, p=0.039) and PSA density (r=0.156, p=0.005). Ca/Mg ratio was a preoperative predictor of high pGS (≥8) according to multiple logistic regression analysis (odds ratio, 1.752; 95% confidence interval, 1.002–3.064; p=0.049). CONCLUSIONS: A high serum Ca/Mg ratio was closely associated with worse clinicopathological parameters (high PSA and PSA density and pGS≥8), suggesting that the Ca/Mg ratio may be a useful serological marker for further characterization of oncologic features in prostate cancer. A multicenter prospective study with long-term follow-up is recommended to further assess the utility of this cost-effective marker as a prognostic indicator of prostate cancer.

Potency of Human Urine-Derived Stem Cells for Renal Lineage Differentiation

Kidney is one of the most difficult organs for regeneration. Several attempts have been performed to regenerate renal tissue using stem cells, the results were not satisfactory. Urine is major product of kidney and contains cells from renal components. Moreover, urine-derived stem cells (USCs) can be easily obtained without any health risks throughout a patient's entire life. Here, we evaluated the utility of USCs for renal tissue regeneration. In this study, the ability of USCs to differentiate into renal lineage cells was compared with that of adipose tissue-derived stem cells (ADSCs) and amniotic fluid-derived stem cells (AFSCs), with respect to surface antigen expression, morphology, immunocytochemistry, renal lineage gene expression, secreted factors, immunomodulatory marker expression, in vivo safety, and renal differentiation potency. Undifferentiated USCs were positive for CD44 and CD73, negative for CD34 and CD45, and formed aggregates after 3 weeks of renal differentiation. Undifferentiated USCs showed high SSEA4 expression, while renal-differentiated cells expressed PAX2, WT1, and CADHERIN 6. In the stem/renal lineageassociated gene analysis, OCT4, SSEA4, and CD117 were significantly downregulated over time, while PAX2, LIM1, PDGFRA, E-CADHERIN, CD24, ACTB, AQP1, OCLN, and NPHS1 were gradually upregulated. In the in vivo safety evaluation, renal-differentiated USCs did not show abnormal histology. These findings demonstrated that USCs have a similar MSC potency, renal lineage-differentiation ability, immunomodulatory effects, and in vivo safety as ADSCs and AFSCs, and showed higher levels of growth factor secretion for paracrine effects. Therefore, urine and USCs can be one of good cell sources for kidney regeneration.

Hypoxia Enhances Cell Properties of Human Mesenchymal Stem Cells

Atmospheric (in vitro) oxygen pressure is around 150 mm Hg (20% O₂), whereas physiologic (in vivo) oxygen pressure ranges between 5 and 50 mm Hg (0.7–7% O₂). The normoxic environment in cell culture does not refer to a physiological stem cell niche. The aim of this study is to investigate the effect of oxygen concentration on cell properties of human mesenchymal stem cells (MSCs). We analyzed cell proliferation rate, senescence, immunophenotype, stemness gene expression and differentiation potency with human urine stem cells (USCs), dental pulp stem cells (DPSCs), amniotic fluid stem cells (AFSCs), and bone marrow stromal cells (BMSCs). USCs, DPSCs, AFSCs and BMSCs were cultured under either 5% O₂ hypoxic or 20% O₂ normoxic conditions for 5 days. MSCs cultured under hypoxia showed significantly increased proliferation rate and high percentage of S-phase cells, compared to normoxic condition. In real-time PCR assay, the cells cultured under hypoxia expressed higher level of Oct4, C-Myc, Nanog, Nestin and HIF-1α. In immunophenotype analysis, MSCs cultured under hypoxia maintained higher level of the MSC surface markers, and lower hematopoietic markers. Senescence was inhibited under hypoxia. Hypoxia enhances osteogenic differentiation efficiency compared to normoxia. Hypoxia showed enhanced cell proliferation rate, retention of stem cell properties, inhibition of senescence, and increased differentiation ability compared to normoxia.

Comparison of 5 Different Rat Models to Establish a Standard Animal Model for Research Into Interstitial Cystitis / 대한배뇨장애요실금학회지

PURPOSE: We evaluated 5 different rat models using different agents in order to establish a standard animal model for interstitial cystitis (IC) in terms of the functional and pathologic characteristics of the bladder. METHODS: Five IC models were generated in 8-week-old female Sprague-Dawley rats via transurethral instillation of 0.1M hydrogen chloride (HCl) or 3% acetic acid (AA), intraperitoneal injection of cyclophosphamide (CYP) or lipopolysaccharide (LPS), or subcutaneous injection of uroplakin II (UPK2). After generating the IC models, conscious cystometry was performed on days 3, 7, and 14. All rats were euthanized on day 14 and their bladders were obtained for histological and pro-inflammatory-related gene expression analysis. RESULTS: In the cystometric analysis, all experimental groups showed significantly decreased intercontraction intervals compared with the control group on day 3, but only the LPS and UPK groups maintained significantly shorter intercontraction intervals than the control group on day 14. The histological analysis revealed that areas with severe urothelial erosion (HCl, AA, and UPK) and hyperplasia (CYP and LPS), particularly in the UPK-treated bladders, showed a markedly increased infiltration of toluidine blue-stained mast cells and increased tissue fibrosis. In addition, significantly elevated expression of interleukin-1b, interleukin-6, myeloperoxidase, monocyte chemotactic protein 1, and Toll-like receptors 2 and 4 was observed in the UPK group compared to the other groups. CONCLUSIONS: Among the 5 different agents, the injection of UPK generated the most effective IC animal model, showing consequent urothelial barrier loss, inflammatory reaction, tissue fibrosis stimulation, and persistent hyperactive bladder.

Comparison of Surgical Outcomes Between Holmium Laser Enucleation and Transurethral Resection of the Prostate in Patients With Detrusor Underactivity / 대한배뇨장애요실금학회지

PURPOSE: Currently, holmium laser enucleation of the prostate (HoLEP) and transurethral resection of the prostate (TURP) are the standard surgical procedures used to treat benign prostatic hyperplasia (BPH). Several recent studies have demonstrated that the surgical management of BPH in patients with detrusor underactivity (DU) can effectively improve voiding symptoms, but comparative data on the efficacy of HoLEP and TURP are insufficient. Therefore, we compared the short-term surgical outcomes of HoLEP and TURP in patients with DU. METHODS: From January 2010 to May 2015, 352 patients underwent HoLEP or TURP in procedures performed by a single surgeon. Of these patients, 56 patients with both BPH and DU were enrolled in this study (HoLEP, n=24; TURP, n=32). Surgical outcomes were retrospectively compared between the 2 groups. DU was defined as a detrusor pressure at maximal flow rate of <40 cm H(2)O as measured by a pressure flow study. RESULTS: The preoperative characteristics of patients and the presence of comorbidities were comparable between the 2 groups. The TURP group showed a significantly shorter operative time than the HoLEP group (P=0.033). The weight of the resected prostate was greater in the HoLEP group, and postoperative voiding parameters, including peak flow rate and postvoid residual urine volume were significantly better in the HoLEP group than in the TURP group. CONCLUSIONS: HoLEP can be effectively and safely performed in patients with DU and can be expected to have better surgical outcomes than TURP in terms of the improvement in lower urinary tract symptoms.

Target Molecule Expression Profiles in Metastatic Renal Cell Carcinoma: Development of Individual Targeted Therapy

The aim of this study is to analyze the level of target molecule expression in metastatic renal cell carcinoma (RCC) to determine whether there is a correlation between molecular marker expression and clinical response. Ten patients with metastatic RCC, who received receptor tyrosine kinase (RTK) targeted therapy after cytoreductive or radical nephrectomy, were included. The expression of target molecules relating to the RTK, mammalian target of rapamycin, hypoxia inducible factor, mitogen activated protein kinase, and adenosine monophosphate-activated protein kinase pathways were analyzed using real-time polymerase chain reaction and immunohistochemistry. We correlated the level of target molecule expression with clinical response, including efficacy and adverse events experience during RTK targeted therapy. All patients showed similar histological subtype and grade on pathological examination; however, the expression of RCC target molecules was very different among the patients. The expression of molecules related to the RTK pathway in RCC tissue as well as relative expression of molecules in RCC tissue compared to normal kidney tissue, were higher in patients who showed a good response to RTK targeted therapy compared to those that showed a poor response. Target molecule expression in normal kidney tissue was higher in patients who experienced high-grade adverse events than in patients who experienced low-grade events. Target molecule expression in metastatic RCC correlates with targeted therapy clinical response including efficacy and adverse events. Personalized target molecule expression profiles could be used to predict clinical response to different targeted therapies, thus helping optimization of targeted therapies for patients with metastatic RCC.