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This study investigated the effects of adipose-derived stem cell sheets on a rat model of detrusor underactivity.Adipose-derived stem cell sheets were prepared from the subcutaneous adipose tissue of male Lewis rats. Female Lewis rats were assigned into four groups: control, sham operation, cryo-injury, and cryo-injury+sheet (n = 8 per group). Rats in the cryo-injury+sheet group were implanted with ASC sheets 3 days after cryo-injury induction and underwent cystometry 7 days later. Subsequently, reverse transcription-polymerase chain reaction (RT-PCR) and histopathological examinations were performed. Cell sheets expressing the green fluorescent protein were prepared and transplanted to confirm the viability and differentiation of the sheets. Fluorescence was confirmed using a fluorescence stereomicroscope on days 3, 7, 14, 21, and 28 after sheet implantation, and tissue immunostaining was performed.Cystometry showed that sheet implantation improved the maximum intravesical pressure (P = 0.009) and the residual urine volume (P = 0.011). Furthermore, RT-PCR indicated that the mRNA levels of the angiogenic factors vascular endothelial growth factor and hepatocyte growth factor were significantly higher in the cryo-injury+sheet group than in the cryo-injury group (P = 0.045, P = 0.037, respectively). Histologically, sheet implantation resulted in an improvement in inflammation and increased the number of blood vessels. Green fluorescent protein-positive cells fused with von Willebrand factor-positive cells and differentiated into blood vessels 7 days after sheet implantation.Adipose-derived stem cell sheets transplanted into the bladder of cryo-injured rats differentiated into blood vessels and restored bladder contractile function 7 days after transplantation.

OBJECTIVE: To assess the functional role of Hyperpolarization-activated cyclic nucleotide-gated gated channel (HCN) subtypes in the aging bladder phenotype characterized by diminished bladder volume sensation (BVS) with or without the detrusor instability (DI). METHODS: Expression of HCN subtypes was examined by quantitative RT-PCR and Western blot in aged male Fisher 344 rats (n=15) and young rats (n=15). Nocturnal urination and awake cystometry (CMG) were assessed in presence and absence of a steady state HCN channel blockade achieved with daily oral gavage of vehicle or Ivabradine (HCN blocker) 6mg/kg for 7 days. RESULTS: The association of BVS with the age-related downregulation (~30%) of cAMP sensitive HCN1, HCN2 subtypes, and (~50%) upregulation of cAMP insensitive HCN3 subtype is evinced by a doubling in the mean urine volume of nocturnal voids (0.82 ±0.22 mL vs 0.41 ±0.12 mL; n=10; p < 0.05) predicting an age-related rise in micturition volume threshold (p

Aims Aging is an obvious risk factor for detrusor underactivity. We investigated the effects of aging on bladder function in spontaneously hypertensive rats. Main methods Male spontaneously hypertensive rats and Wistar Kyoto rats (used as normotensive controls) at the ages of 18, 36, 54, or 72 weeks were used. Bladder weight, blood pressure, bladder blood flow, and urodynamic and renal parameters were measured. Additionally, detrusor thickness and renal histology were evaluated. Key findings In spontaneously hypertensive rats, significant increases were observed in bladder weight/body weight ratio, blood pressure, detrusor thickness, intercontraction interval, urine output, serum creatinine, and renal glomerular and tubular scores, and decreases in bladder blood flow and urine osmolality at 72 weeks as compared to those at 18 weeks. In spontaneously hypertensive rats, significant increases were observed in single voided volume, post voiding residual urine volume, and bladder capacity, with decrease in voiding efficiency were observed at 54 or 72 weeks than at 18 weeks. However, there were no significant differences in blood pressure, urodynamic and renal parameters, detrusor thickness and renal histology among Wistar Kyoto rats of different ages. Significance In spontaneously hypertensive rats, aging induces significant increases in blood pressure, single voided volume, post voiding residual urine volume, intercontraction intervals and urine output, and decreases in voiding efficiency and bladder blood flow indicative of detrusor underactivity. Aging-related severe hypertension could induce voiding dysfunction such as detrusor underactivity via severe bladder ischemia and polyuria. Aged spontaneously hypertensive rats may be useful animal models for detrusor underactivity.

OBJECTIVE: To evaluate whether approved gastroprokinetic agent, acotiamide exerts a direct excitatory effect in bladder to help explain the reported meaningful reduction of post-void residual urine volume (PVR) in detrusor underactivity (DU) patients after thrice daily oral intake of acotiamide 100 mg for 2 weeks. METHODS: Effect of acotiamide [1–16μM] was assessed on nerve-mediated contractions evoked by electrical field stimulation (EFS) for 5s with 5ms pulse trains of 10V in longitudinal, mucosa intact rat and human bladder strips to construct frequency response curve (1–32Hz) and repeat 10Hz stimulation at 60s interval. Effect of acotiamide 2μM on spontaneous and carbachol evoked contractions was also assessed. RESULTS: Acotiamide 2μM significantly enhanced the Atropine and Tetrodotoxin (TTX)-sensitive EFS evoked contractions of rat and human bladder at 8–32Hz (Two-way ANOVA followed Sidak’s multiple comparison; *p