Development of new therapy for bladder dysfunction:Combined approaches of phamiacology and tissue engineering

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1) The threshold measurement for intravesical urothelial electric stimulation with three different frequencies revealed that Patients with interstitial cystitis (IC) had significantly lower threshold for C-fiber afferents stimulation than those with benign prostatic hyperplasia.2) The clinical and urodynamic effects of intravesical instillation of resiniferatoxin (RTX) were investigated in 5 patients with detrusor overactivity (DO) and 6 patients with interstitial cystitis (IC) resistant against standard conservative therapy. Four of 5 DO patients responded to the treatment within 1 week after the instillation, and the effect lasted for 3-9 months. Five of 6 IC patients showed improvement of their storage symptoms within 1 week after the treatment, and bladder pain score and mean voided volume were significantly improved. However, these effects disappeared within 1-2 months. No adverse events were reported.3) In rats, intravesical ATP, an agonist for P2X3 receptors, decreased bladder c … More apacity and threshold pressure for voiding, which was associated with an increase in the afferent activity of RTX-resistant C-fibers of the primary bladder afferents. Theses results suggest that activation of P2X3 receptors facilitates RTX-resistant C-fibers in the rat bladder.4) Bladder augmentation in rats using human amniotic membrane (hAM) revealed regeneration of urothelium, detrusor smooth muscle, and nerve fibers in the graft within 3 months postoperatively. The hAM-augmented bladders displayed adequate capacity and compliance, indicating that human amniotic membrane can be used as a scaffold for bladder augmentation. We have also found that in nude mice, bone marrow-derived cells, when implanted into freeze-injured urinary bladders, can differentiate into smooth muscle cells and reconstruct smooth muscle layers.5) All together, the results of the present studies indicate that bladder dysfunction can be treated with various pharmacological agents targeting urothelial-afferent neurotransduction system of the bladder as well as tissue engineering techniques using human amniotic membrane and bone marrow-derived cells. Less