Changes in uroplakin expression in the urothelium of patients with ulcerative interstitial cystitis/bladder pain syndrome.

Purpose: We evaluated changes in the expression of uroplakin (UP) in the urothelium of patients with ulcerative interstitial cystitis/bladder pain syndrome (IC/BPS). Materials and Methods: Bladder samples were collected from 19 patients with ulcerative IC/BPS who were treated with augmentation ileocystoplasty and from 5 control patients. Frequency-volume charts, the pain visual analogue scale (VAS), and the O'Leary-Sant interstitial cystitis symptom index (ICSI) and problem index (ICPI) were used to evaluate the patients' symptoms preoperatively. The expression levels of UP-Ib and UP-III in the urothelium were compared between the IC/BPS patients and control patients. Results: Sixteen women and three men with IC/BPS were evaluated. Their values for preoperative mean voiding frequency, number of nocturia episodes, and functional bladder capacity as recorded in frequency-volume charts were 21.1±12.8, 5.9±4.2, and 151.1±62.7 mL, respectively. The mean pain VAS, ICSI, and ICPI scores were 8.4±1.3, 17.7±2.2, and 14.7±1.8, respectively. Immunofluorescence staining showed that UP-Ib and UP-III were localized in the urothelium. Upon Western blot analysis, the expression of UP-III was significantly increased in the IC/BPS group compared with the control group. However, expression of UP-Ib did not differ significantly between the IC/BPS and control groups. Conclusions: UP-III was significantly upregulated in patients with ulcerative IC/BPS. UP-III is a potential biomarker for the diagnosis of ulcerative IC/BPS.

Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium.

For augmentation or reconstruction of urinary bladder after cystectomy, bladder urothelium derived from human induced pluripotent stem cells (hiPSCs) has recently received focus. However, previous studies have only shown the emergence of cells expressing some urothelial markers among derivatives of hiPSCs, and no report has demonstrated the stratified structure, which is a particularly important attribute of the barrier function of mature bladder urothelium. In present study, we developed a method for the directed differentiation of hiPSCs into mature stratified bladder urothelium. The caudal hindgut, from which the bladder urothelium develops, was predominantly induced via the high-dose administration of CHIR99021 during definitive endoderm induction, and this treatment subsequently increased the expressions of uroplakins. Terminal differentiation, characterized by the increased expression of uroplakins, CK13, and CK20, was induced with the combination of Troglitazone + PD153035. FGF10 enhanced the expression of uroplakins and the stratification of the epithelium, and the transwell culture system further enhanced such stratification. Furthermore, the barrier function of our urothelium was demonstrated by a permeability assay using FITC-dextran. According to an immunohistological analysis, the stratified uroplakin II-positive epithelium was observed in the transwells. This method might be useful in the field of regenerative medicine of the bladder.