Intravenously engrafted human multilineage-differentiating stress-enduring (Muse) cells rescue erectile function after rat cavernous nerve injury.

OBJECTIVE: To evaluate the effect of intravenous administration of human multilineage-differentiating stress-enduring (Muse) cells on rat postoperative erectile dysfunction (ED) with cavernous nerve (CN) injury without an immunosuppressant. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomised into three groups after CN crush injury. Either human-Muse cells, non-Muse mesenchymal stem cells (MSCs) (both 1.0 × 105 cells), or vehicle was infused intravenously at 3 h after CN injury without immunosuppressant. Erectile function was assessed by measuring intracavernous pressure (ICP) and arterial pressure (AP) during pelvic nerve electrostimulation 28 days after surgery. At 48 h and 28 days after intravenous infusion of Muse cells, the homing of Muse cells and non-Muse MSCs was evaluated in the major pelvic ganglion (MPG) after CN injury. In addition, expressions of C-X-C motif chemokine ligand (Cxcl12) and glial cell line-derived neurotrophic factor (Gdnf) in the MPG were examined by real-time polymerase chain reaction. Statistical analyses and comparisons among groups were performed using one-way analysis of variance followed by the Tukey test for parametric data and Kruskal-Wallis test followed by the Dunn-Bonferroni test for non-parametric data. RESULTS: The mean (SEM) ICP/AP values at 28 days were 0.51 (0.02) in the Muse cell group, 0.37 (0.03) in the non-Muse MSC group, and 0.36 (0.04) in the vehicle group, showing a significant positive response in the Muse cell group compared with the non-Muse and vehicle groups (P = 0.013 and P = 0.010, respectively). In the MPG, Muse cells were observed to be engrafted at 48 h and expressed Schwann cell markers S100 (~46%) and glial fibrillary acidic protein (~24%) at 28 days, while non-Muse MSCs were basically not engrafted at 48 h. Higher gene expression of Cxcl12 (P = 0.048) and Gdnf (P = 0.040) was found in the MPG of the Muse group than in the vehicle group 48 h after infusion. CONCLUSION: Intravenously engrafted human Muse cells recovered rat erectile function after CN injury in a rat model possibly by upregulating Cxcl12 and Gdnf.

Impact of Tissue Sealing Sheet on Erectile Dysfunction in a Rat Model of Nerve-Sparing Radical Prostatectomy.

INTRODUCTION: The tissue sealing sheet has recently been used to prevent intraoperative bleeding from the neurovascular bundles in radical prostatectomy. Surgical stress or inflammatory changes likely play a role in erectile dysfunction after cavernous nerve injury. However, the efficacy of a tissue sealing sheet for preventing erectile function after nerve-sparing radical prostatectomy remains unclear. AIM: To evaluate the effect of a tissue sealing sheet on erectile dysfunction after cavernous nerve dissection. METHODS: Male Sprague-Dawley rats were randomly divided into three groups and subjected to sham operation or bilateral cavernous nerve dissection with (sheet group) or without (non-sheet group) a tissue sealing sheet. In the sheet group, cavernous nerves were sealed with a tissue sealing sheet immediately after cavernous nerve dissection. MAIN OUTCOME MEASURES: Erectile function was assessed by measuring intracavernous pressure and arterial pressure during pelvic nerve electrostimulation at 4 weeks after surgery. Expressions of interleukin-6, tumor growth factor-ß1, and heme-oxygenase-1 in the major pelvic ganglion were examined by real-time polymerase chain reaction. RESULTS: Mean intracavernous pressure along with mean arterial pressure in the sheet group were similar to those in the sham group and showed a significant positive response compared with the non-sheet group (P < .05). Furthermore, expressions of interleukin-6, tumor growth factor-ß1, and heme-oxygenase-1 were significantly lower in the sheet group than in the non-sheet group (P < .05). CONCLUSION: Use of a tissue sealing sheet attenuated postoperative inflammatory changes and oxidative stress and improved erectile function after cavernous nerve injury in rats. The tissue sealing sheet might become a useful therapeutic approach to preserve erectile function after nerve-sparing radical prostatectomy.

Liposome Based Intravesical Therapy Targeting Nerve Growth Factor Ameliorates Bladder Hypersensitivity in Rats with Experimental Colitis.

PURPOSE: Pelvic organ cross sensitization is considered to contribute to overlapping symptoms in chronic pelvic pain syndrome. Nerve growth factor over expression in the bladder is reportedly involved in the symptom development of bladder pain syndrome/interstitial cystitis. We examined whether a reduction of over expressed nerve growth factor in the bladder by intravesical treatment with liposome and oligonucleotide conjugates would ameliorate bladder hypersensitivity in a rat colitis model. MATERIALS AND METHODS: Adult female rats were divided into 1) a control group, 2) a colitis-oligonucleotide group with intracolonic TNBS (2,4,6-trinitrobenzene sulfonic acid) enema and intravesical liposome-oligonucleotide treatments, 2) a colitis-saline group with intracolonic TNBS and intravesical saline treatments, 4) a sham oligonucleotide group with intravesical liposome-oligonucleotide treatment without colitis and 5) a sham-saline group with intravesical saline treatment without colitis. Liposomes conjugated with nerve growth factor antisense oligonucleotide or saline solution were instilled in the bladder and 24 hours later colitis was induced by TNBS enema. Effects of nerve growth factor antisense treatment were evaluated by pain behavior, cystometry, molecular analyses and immunohistochemistry 10 days after TNBS treatment. RESULTS: In colitis-oligonucleotide rats nerve growth factor antisense treatment ameliorated pain behavior and decreased a reduction in the intercontraction interval in response to acetic acid stimulation as well as nerve growth factor expression in the bladder mucosa. All were enhanced in colitis-saline rats compared to sham rats. CONCLUSIONS: Nerve growth factor over expression in the bladder mucosa and bladder hypersensitivity induced after colitis were decreased by intravesical application of liposome-oligonucleotide targeting nerve growth factor. This suggests that local antinerve growth factor therapy could be effective treatment of bladder symptoms in chronic pelvic pain syndrome.

Radical prostatectomy for high-risk prostate cancer: biochemical outcome.

OBJECTIVES: To determine the biochemical outcome following radical prostatectomy alone in patients with high-risk prostate cancer. METHODS: Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre-operative data, we stratified the patients into low, intermediate, and high-risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate-specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL. RESULTS: The PSA failure-free survival rate for the high-risk group (n = 46) was 64.5% after a median follow-up period of 39 months. Among patients with high-risk disease, none with pathologically organ-confined cancer (n = 19) and a negative surgical margin had PSA failure. The PSA failure-free rate in patients with non organ-confined cancer (n = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) >or=30 was a significant independent predictor of extra prostatic extension. CONCLUSIONS: Radical prostatectomy is feasible in high-risk prostate cancer patients, only if they have a pathologically organ-confined disease.