Basic Research - Neurourology & LUTS/BPH & Others(구연) (E-037)

Evaluation of stem cell treatment efficacy in chronic bladder ischemia-induced rat model
Urology, Asan Medical Center, University of Ulsan College of Medicine, Urology, Asan Medical Center, University of Ulsan College of Medicine, Urology, Asan Medical Center, University of Ulsan College of Medicine, Urology, Asan Medical Center, University of Ulsan College of Medicine, Department of Biomedical Sciences, University of Ulsan College of Medicine, Urology, Asan Medical Center, University of Ulsan College of Medicine
Hwan Yeul Yu, Jung-Hyun Shin, Chae-Min Ryu, Jaebeom Jun, Dong-Myung Shin, Myung-Soo Choo
Background: We developed a detrusor underactivity (DUA) rat model with atherosclerosis-induced chronic bladder ischemia (CBI) and evaluated the therapeutic effects of human embryonic stem cell derived multipotent stem cells (M-MSCs). / Objectives: We tried to develop a rat model of atherosclerosis-induced chronic bladder ischemia (CBI) and investigate the effect of chronic bladder ischemia on bladder function. Recently, as stem cell research presents new possibilities for treating previously intractable disorders, stem cell-based therapy has also been proposed as a novel therapeutic approach for incurable bladder disorders, including stress urinary incontinence, overactive bladder, detrusor underactivity, and bladder or urethral injury. Also, we reported beneficial outcomes of adult tissues derived mesenchymal stem cells (MSCs) for treating Chronic Bladder Ischemia rat model which is a chronic inflammatory condition of the bladder. However, direct assessment of the biological and molecular properties of engrafted cells in the pathological environment has not been performed for current MSC therapies. We tried to evaluate bladder function and pathological efficacy through stem cell therapy of chronic bladder ischemia rat model. / Materials and Methods: 16-week old male Sprague–Dawley rats were divided into five groups (n=10). DUA group underwent endothelial injury of the iliac arteries 30 times to induce CBI and received a 2% cholesterol diet. The sham group underwent sham operation and received a 1.25% cholesterol diet. 7 weeks after endothelial injury, submucosal layer of the anterior wall and dome of the bladder was injected with M-MSCs (250k, 500k, 1,000k) or phosphate-buffer solution (sham). One week after M-MSC injection, awake cystometry was performed and bladder was harvested for histological analysis and organ bath study. / Results and Conclusion: Results: CBI by iliac artery injury and high fat diet induced DUA; micturition pressure was significantly lower with increased micturition interval and larger residual volume. DUA profiles were improved dose-dependently in stem cell groups with best efficacy in 1,000k group. On histological analysis, DUA group presented decreased muscle layer (anti-alpha smooth muscle actin antibody) and increased collagen deposit in detrusor (Masson’s trichrome staining). 1,000k stem cell injection significantly restored the muscle layer and alleviated fibrosis.   Conclusions: Single injection of M-MSC directly to the bladder improved voiding profiles and histology of CBI induced DUA rat model in dose-dependent manners with significant efficacy in 1,000k group. Restoration of bladder muscle layer and decreased collagen deposits seems to result in alleviation of DUA. Further investigation is needed.
keywords : Detrusor underactivity; Chronic Bladder Ischemia, human embryonic stem cell derived multipotent stem cells (M-MSCs)

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