Urethral injection of dedifferentiated fat cells ameliorates sphincter damage and voiding dysfunction in a rat model of persistence stress urinary incontinence.

PURPOSE: Dedifferentiated fat (DFAT) cells are mature adipocyte-derived multipotent cells that can be applicable to cell-based therapy for stress urinary incontinence (SUI). This study developed a persistence SUI model that allows long-term evaluation using a combination of vaginal distention (VD) and bilateral ovariectomy (OVX) in rats. Then, the therapeutic effects of DFAT cell transplantation in the persistence SUI model was examined. METHODS: In total, 48 Sprague-Dawley rats were divided into four groups and underwent VD (VD group), bilateral OVX (OVX group), VD and bilateral OVX (VD + OVX group), or sham operation (Control group). At 2, 4, and 6 weeks after injury, leak point pressure (LPP) and histological changes of the urethral sphincter were evaluated. Next, 14 rats undergoing VD and bilateral OVX were divided into two groups and administered urethral injection of DFAT cells (DFAT group) or fibroblasts (Fibroblast group). At 6 weeks after the injection, LPP and histology of the urethral sphincter were evaluated. RESULTS: The VD + OVX group retained a decrease in LPP with sphincter muscle atrophy at least until 6 weeks after injury. The LPP and urethral sphincter muscle atrophy in the DFAT group recovered better than those in the fibroblast group. CONCLUSIONS: The persistence SUI model was created by a combination of VD and bilateral OVX in rats. Urethral injection of DFAT cells inhibited sphincter muscle atrophy and improved LPP in the persistence SUI model. These findings suggest that the DFAT cells may be an attractive cell source for cell-based therapy to treat SUI.

Transplantation of mature adipocyte-derived dedifferentiated fat cells for the treatment of vesicoureteral reflux in a rat model.

PURPOSE: Autologous cells potentially provide an ideal injectable substance for management in vesicoureteral reflux (VUR). The aim of this study is to examine the effects of mature adipocyte-derived dedifferentiated fat (DFAT) cell transplantation on VUR in a rat bladder pressurization-induced VUR model. METHODS: To create VUR, Sprague-Dawley rats underwent urethral clamping and placement of cystostomy followed by intravesical pressurization. Rat DFAT cells (1 × 106 cells, DFAT group, n = 5) or saline (control group, n = 5) was then injected into the bilateral vesicoureteral junctions. Two weeks later, VUR grade was evaluated on cystography. The number of apoptotic cells in the renal pelvic urothelium, the ureteral inner/outer diameter ratio and the area of connective tissue in the posterior bladder wall were measured. RESULTS: The reflux grade in the DFAT group was significantly lower than that in the control group. The number of apoptotic cells in the renal pelvic urothelium, ureteral inner/outer diameter ratio and connective tissue area in DFAT group were significantly lower in comparison with the control group. CONCLUSIONS: DFAT cell transplantation improved VUR and exerted nephroprotective effects in a rat VUR model.

Efficacy of transurethral prostate enucleation by bipolar system for patients with benign prostatic hyperplasia.

BACKGROUND: The aim of this paper was to evaluate the efficacies and safety of transurethral prostate enucleation by bipolar system (TUEB) for the patients with benign prostatic hyperplasia (BPH). METHODS: We prospectively evaluated clinical outcomes of TUEB in 55 patients with BPH from July 2005 to January 2011. Mean ages of the patients were 69.2 years. International Prostate Symptom Score (IPSS), IPSS-quality of life (IPSS-QOL) were assessed before and 12 months after surgery. Serum PSA, maximal flow rate (MFR), and post-void residual (PVR) were also evaluated before and 6 and 12 months after surgery. RESULTS: The median prostate volumes and resection volumes were 64.1 g (interquartile range [IQR]: 48-87) and 34.4 g (25-60.2), respectively. The median operation time was 138.0 min (100.2-169.2). Total IPSS scores and IPSS-QOL were significantly improved (from 24 [17-31] to 5 [2-8] points, and from 6 [5-6] to 2 [1-2] points, both P<0.001). MFR and PVR were significantly improved 6 and 12 months after TUEB (from 6.2 [3.9-8.3] to 15.1 [10.5-20.9], and 14.6 [10.2-20.5] mL/s, P<0.0001, and from 151.5 [81.5-284.7] to 16.5 [0-30.5], and 6.0 [0-41.0] mL, P<0.0001, respectively). Serum PSA also significantly decreased, 6 and 12 months (from 7.5 [4.7-9.8] to 1.1 [0.5-1.5], and 0.6 [0.3-1.9] ng/mL, P<0.0001). Although hemoglobin decreased after operation, no case experienced blood transfusion. Three episodes of urinary tract infections, 14 cases of mild stress urinary incontinence, 2 cases of urinary retention were occurred transiently with recovery within 1 month after surgery. CONCLUSIONS: We identified favorable efficacy and safety of TUEB. TUEB appears to be another possibility in the treatment of BPH.

Transplantation of mature adipocyte-derived dedifferentiated fat (DFAT) cells improves urethral sphincter contractility in a rat model.

OBJECTIVES: To examine the effects of mature adipocyte-derived dedifferentiated fat (DFAT) cell transplantation on urethral tissue regeneration and sphincter function. METHODS: Sixteen female Sprague-Dawley rats underwent vaginal distension (VD) for 3 h. Subsequently, green fluorescence protein (GFP)-labeled DFAT cells (1×10(6) in 20 µL saline, DFAT group, n=8) or saline (20 µL, control group, n=8) were injected into paraurethral connective tissue. Two weeks following VD, leak point pressure (LPP) was measured and an immunohistochemical analysis of the urethra was performed to evaluate urethral sphincter regeneration. RESULTS: The VD model was characterized by atrophy of the urethral sphincter and showed a decrease in LPP. DFAT cell transplantation resulted in a significant improvement of LPP (DFAT group: 37.3±6.4 vs control group: 21.7±5.7 mmHg, P<0.01). Immunohistochemistry revealed that the striated muscle thickness and smooth muscle α-actin-positive area were significantly (P<0.05) larger in the DFAT group than in the control group. DFAT cell transplantation enhanced macrophage accumulation followed by an increased number of cells in the proliferative state. Transplanted DFAT cells were observed in the damaged smooth muscle layer and showed positive staining for smooth muscle α-actin, suggesting conversion into the smooth muscle cell phenotype. CONCLUSIONS: DFAT cell transplantation promotes sphincter muscle regeneration and improves LPP in the rat VD model.