Yun Seob Song

Mesenchymal stem cells overexpressing hepatocyte growth factor (HGF) inhibit collagen deposit and improve bladder function in rat model of bladder outlet obstruction.

Bladder outlet obstruction (BOO) caused by collagen deposit is one of the most common problems in elderly male. This study was performed to examine the capability of human mesenchymal stem cells (MSCs) overexpressing hepatocyte growth factor (HGF) to inhibit collagen deposition in rat model of bladder outlet obstruction (BOO). HGF is known for its antifibrotic effect and the most promising agent for treating bladder fibrosis. BM3.B10 stable immortalized human MSC line (B10) was transduced to encode human HGF with a retroviral vector was prepared (B10.HGF). Two weeks after the onset of BOO, B10, and B10.HGF cells were injected into the rats bladder wall. After 4 weeks, bladder tissues were harvested and Massons trichrome staining was performed. Transgene expression in HGF-expressing B10 cells was demonstrated by reverse transcriptase polymerase chain reaction and immunohistochemical staining, and the high levels of HGF secreted by B10. HGF cells was confirmed by ELISA. The mean bladder weight in BOO rats was 5.8 times of the normal controls, while in animals grafted with B10.HGF cells, the weight was down to four times of the control [90.2 ± 1.6 (control), 89.9 ± 2.8 (sham), 527.9 ± 150.9 (BOO), 447.7 ± 41.0 (BOO + B10), and 362.7 ± 113.2 (BOO + B10. HGF)]. The mean percentage of collagen area increased in BOO rats, while in the animals transplanted with B10.HGF cells, the collagen area decreased to the normal control level [12.2 ± 1.3, (control), 12.8 ± 1.1 (sham), 26.6 ± 2.7 (BOO), 19.9 ± 6.0 (BOO + B10), and 13.3 ± 2.1 (BOO + B10.HGF)]. The expression of collagen and TGF-β protein increased after BOO, while the expression of HGF and c-met protein increased in the group with B10.HGF transplantation after BOO. Intercontraction interval decreased after BOO, but it recovered after B10.HGF transplantation. Maximal voiding pressure (MVP) increased after BOO, and it recovered to levels of the normal control after transplantation of B10.HGF cells. Residual urine volume (RU) increased after BOO, but the RU increase was not reversed by transplantation of B10.HGF cells. Human MSCs overexpressing HGF inhibited collagen deposition and improved cystometric parameters in bladder outlet obstruction of rats. The present study indicates that transplantation of MSCs modified to overexpress HGF could serve as a novel therapeutic strategy against bladder fibrosis in patients with bladder outlet obstruction.

Stem cell therapy in bladder dysfunction: where are we? And where do we have to go?

To date, stem cell therapy for the bladder has been conducted mainly on an experimental basis in the areas of bladder dysfunction. The therapeutic efficacy of stem cells was originally thought to be derived from their ability to differentiate into various cell types. Studies about stem cell therapy for bladder dysfunction have been limited to an experimental basis and have been less focused than bladder regeneration. Bladder dysfunction was listed in MESH as “urinary bladder neck obstruction”, “urinary bladder, overactive”, and “urinary bladder, neurogenic”. Using those keywords, several articles were searched and studied. The bladder dysfunction model includes bladder outlet obstruction, cryoinjured, diabetes, ischemia, and spinal cord injury. Adipose derived stem cells (ADSCs), bone marrow stem cells (BMSCs), and skeletal muscle derived stem cells (SkMSCs) are used for transplantation to treat bladder dysfunction. The main mechanisms of stem cells to reconstitute or restore bladder dysfunction are migration, differentiation, and paracrine effects. The aim of this study is to review the stem cell therapy for bladder dysfunction and to provide the status of stem cell therapy for bladder dysfunction.

Inhibition of Collagen Deposit in Obstructed Rat Bladder Outlet by Transplantation of Superparamagnetic Iron Oxide-Labeled Human Mesenchymal Stem Cells as Monitored by Molecular Magnetic Resonance Imaging (MRI)

Bladder outlet obstruction (BOO) caused by collagen deposit is one of the most common problems in elderly males. The present study is to investigate if human mesenchymal stem cells (MSCs) are capable of inhibiting collagen deposition and improve cystometric parameters in bladder outlet obstruction in rats. Human MSCs were labeled with nanoparticles containing superparamagnetic iron oxide (SPION), and transplanted in rat BOO lesion site. Forty 6-week-old female Sprague-Dawley rats were divided into four groups (group 1: control, group 2: sham operation, group 3: BOO, and group 4: BOO rats receiving SPION-hMSCs). Two weeks after the onset of BOO, 1 × 106 SPION-hMSCs were injected into the bladder wall. Serial T2-weighted MR images were taken immediately after transplantation of SPION-labeled human MSCs and at 4 weeks posttransplantation. T2-weighted MR images showed a clear hypointense signal induced by the SPION-labeled MSCs. While the expression of collagen and TGF-β protein increased after BOO, the expression of both returned to the original levels after MSC transplantation. Expression of HGF and c-met protein also increased in the group with MSC transplantation. Maximal voiding pressure and residual urine volume increased after BOO but they recovered after MSC transplantation. Human MSCs transplanted in rat BOO models inhibited the bladder fibrosis and mediated recovery of bladder dysfunction. Transplantation of MSC-based cell therapy could be a novel therapeutic strategy against bladder fibrosis in patients with bladder outlet obstruction.

Influence of prostatic calculi on lower urinary tract symptoms in middle-aged men.

OBJECTIVES To investigate the incidence and echographic patterns of prostatic calculi, and to determine whether the presence of prostatic calculi is an associated factor for moderate lower urinary tract symptom (LUTS) in middle-aged men. METHODS Between October 2007 and June 2010, 1575 consecutive ostensibly healthy Korean men aged 40-59 years visited the health promotion center for a routine check-up and were enrolled. All men had a complete history, physical examination, and an international prostate symptom score (IPSS) questionnaire. Based on the echo patterns of the prostatic calculi by transrectal ultrasound, the men were divided in 3 groups-no calculi; type A calculi (discrete, small echoes); and type B calculi (large masses of multiple echoes, much coarser). RESULTS In total, 1563 men were included. Measurable calcifications in the prostate gland were found in 799 men (51.1%). Small calculi (type A) were found in 615 men (39.3%) and large calculi (type B) were found in 184 men (11.8%). In the multivariate analysis, old age (>50 years), obesity (body mass index >25 kg/m(2)), and large calculi (type B) were significant associated factors for higher IPSS ≥8. The likelihood of IPSS being ≥8 was related to large calculi group with a 1.784-fold increase in risk over no and small calculi (P <.001). CONCLUSIONS The presence of large prostatic calculi is a significant associated factor of moderate LUTS, whereas there was no statistical difference in IPSS analyzed between the no calculi and small calculi group.

Treatment of Bladder Dysfunction Using Stem Cell or Tissue Engineering Technique

Tissue engineering and stem cell transplantation are two important options that may help overcome limitations in the current treatment strategy for bladder dysfunction. Stem cell therapy holds great promise for treating pathophysiology, as well as for urological tissue engineering and regeneration. To date, stem cell therapy in urology has mainly focused on oncology and erectile dysfunction. The therapeutic potency of stem cells (SCs) was originally thought to derive from their ability to differentiate into various cell types including smooth muscle. The main mechanisms of SCs in reconstituting or restoring bladder function are migration, differentiation, and paracrine effects. Nowadays, paracrine effects of stem cells are thought to be more prominent because of their stimulating effects on stem cells and adjacent cells. Studies of stem cell therapy for bladder dysfunction have been limited to experimental models and have been less focused on tissue engineering for bladder regeneration. Bladder outlet obstruction is a representative model. Adipose-derived stem cells, bone marrow stem cells (BMSCs), and skeletal muscle-derived stem cells or muscle precursor cells are used for transplantation to treat bladder dysfunction. The aim of this study is to review stem cell therapy and updated tissue regeneration as treatments for bladder dysfunction and to provide the current status of stem cell therapy and tissue engineering for bladder dysfunction including its mechanisms and limitations.

Sexual Function and Quality of Life in Korean Women with Chronic Renal Failure on Hemodialysis: Case-Control Study

OBJECTIVE To assess sexual function and quality of life (QOL) in Korean women with chronic renal failure (CRF) receiving hemodialysis. METHODS Between March 2006 and February 2007, we enrolled 38 consecutive patients between 30 and 64 years old (mean age, 46.1 years old). We enrolled 37 age-matched individuals who visited health promotion center in the study as controls. All were evaluated for estradiol, testosterone, prolactin, and follicle-stimulating hormone (FSH) levels. To obtain sexual function and QOL assessments, the patients and controls were asked to fill out the Female Sexual Function Index (FSFI) and the Medical Outcomes Study Short Form (SF-36). RESULTS The rate of menopause was significantly different between groups (78.9% in the patient group and 27.0% in the control group, P <0.001). The patient group had lower levels of estradiol and testosterone and higher levels of prolactin and FSH than the control groups (all P <0.05). Of the six domains in the FSFI questionnaire, scores of all domains, namely, desire, arousal, lubrication, orgasm, satisfaction, and pain were significantly lower in the patient group than in the control group (all P <0.05). Regarding the SF-36, the patient group had lower scores on physical functioning, role-physical functioning, role-emotional functioning, vitality, and general health perception (all P <0.05). CONCLUSIONS Hormone disturbances and early menopause are common in Korean women with CRF receiving hemodialysis. In addition, our findings suggest that these patients have higher disturbances in sexual function and QOL than the normal population.

Hepatocyte-Like Cells from Human Mesenchymal Stem Cells Engrafted in Regenerating Rat Liver Tracked with In Vivo Magnetic Resonance Imaging

Cell transplantation using hepatocytes derived from stem cells has been regarded as a possible alternative treatment for various hepatic disorders. Recently, mesenchymal stem cells (MSCs) from the bone marrow have shown the potential to differentiate into hepatocytes in in vitro and in vivo conditions. Noninvasive imaging techniques allowing in vivo assessment of the location of cells are of great value for experimental studies in which these cells are transplanted. We labeled human mesenchymal stem cells (hMSCs) with green fluorescence protein (GFP) and superparamagnetic iron oxide (SPIO) using a transfection agent (GenePORTER). Cellular labeling was evaluated with magnetic resonance (MR) imaging of labeled suspensions, and Prussian blue staining for iron assessment. hMSCs labeled with SPIO and GFP were injected into the portal veins of immunosuppressed, hepatic-damaged rats. MR imaging findings were compared histologically. To identify the differentiation of hMSCs into hepatocytes and to trace the hepatocytes with molecular imaging, we observed the potential of SPIO and GFP double-labeled hMSCs to differentiate into hepatocyte-like cells in the regenerating rat liver. Serial MR imaging showed the possible detection of transplanted cells in the early period of transplantation. Our results indicate that magnetic labeling of hMSCs with SPIO may enable cellular MR imaging and tracking in experimental in vivo settings.

Which Obesity Index Best Correlates With Prostate Volume, Prostate-specific Antigen, and Lower Urinary Tract Symptoms?

OBJECTIVE To determine which measurement variable, waist circumference (WC), body mass index (BMI), or waist-to-hip ratio (WHR) is most closely related to the prostate volume (PV), prostate-specific antigen (PSA), and lower urinary tract symptoms (LUTS). METHODS Between January 2010 and September 2011, 1632 consecutive ostensibly healthy Korean men aged 40-69 years who visited our clinic for a prostate checkup were enrolled into the study. Exclusion criteria included pyuria, history of lower urinary tract disorder influencing urination, and a high PSA level of >3.0 ng/mL. All men underwent a detailed clinical evaluation using the International Prostate Symptom Score (I-PSS) questionnaire. Anthropometric measurements were determined. Serum PSA, urinalysis, and transrectal ultrasound were also performed. RESULTS Data from 1601 men were analyzed. The mean age was 51.6 years, WC 83.7 cm, BMI 24.8 kg/m(2), PV 24.6 mL, and the mean PSA level was 1.07 ng/mL. Using multivariate analysis, PV most positively associated with WC (P < .001), while PSA level had negatively associated with BMI (P = .036) and no significant association with WC or WHR was noted. There was no significant relationship between various obesity indexes and I-PSS. CONCLUSION Our data showed that PV positively associated with central obesity, as represented by WC. In contrast, serum PSA negatively associated with BMI, which represented overall obesity (ie, hemodilution). Our data also suggested that obesity is not associated with lower urinary tract symptoms in Korean men.

Laparoscopic transvesical excision and reconstruction in the management of mid-urethral tape mesh erosion and stones around the bladder neck: initial experiences

Study Type – Prevalence (prospective cohort)

Inhibition of tumor growth and histopathological changes following treatment with a chemokine receptor CXCR4 antagonist in a prostate cancer xenograft model.

The stromal derived factor-1 (SDF-1)/CXCR4 axis is associated with tumor aggressiveness and metastasis in prostate cancer. The present study aimed to explore the potential therapeutic effects of a CXCR4 antagonist in prostate cancer. The effect of SDF-1 and a CXCR4-specific antagonist, AMD3100, on human prostate cancer PC-3 cell proliferation and protein kinase B (Akt) signaling was assessed. Moreover, a PC-3 tumor xenograft model was used to evaluate the effect of AMD3100 on tumor growth and to identify the histopathological changes and immunohistochemical differences between AMD3100-treated and untreated groups. Cell proliferation was not significantly affected by SDF-1 or AMD3100 treatment in vitro. Western blot analysis revealed that SDF-1 stimulation enhanced the expression of phosphorylated Akt in the PC-3 cells, but that the SDF-1-induced expression of phosphorylated Akt was abrogated in the AMD3100-treated PC-3 cells. In the PC-3 tumor xenograft model, AMD3100 significantly inhibited tumor growth, while AMD3100-treated PC-3 tumors had lower levels of microvessel formation and a lower immunoreactivity for the proliferation marker Ki-67 and the anti-apoptotic marker Bcl-2 compared to control tumors in vivo. The CXCR4-specific antagonist inhibits SDF-1-induced CXCR4/Akt signal transduction, and effectively suppresses tumor growth in the PC-3 xenograft model. The present study indicates that CXCR4 targeting may represent a novel strategy for the treatment of castration-resistant prostate cancer (CRPC).