Basic Research - Neurourology & LUTS/BPH & Others(구연) (E-038)

당뇨병성 저활동성 방광 질환에서 인간 배아 줄기 세포 유래 줄기 세포의 치료 효과 : 전임상 연구
서울아산병원 비뇨의학과¹, 울산대학교 의과대학 의생명과학교실²
류채민², 신정현¹, 유환열², 박주현¹, 전재범¹, 신동명², 주명수¹
Purposes
We aimed to establish a rat model with diabetic detrusor underactivity (DUA) and evaluate short-term and long-term therapeutic effect of multipotent mesenchymal stem cells (M-MSCs) derived from human embryonic stem cells.

Materials and methods
Eight-week-old female Sprague-Dawley rats were divided into five groups; sham, DM, 250k, 500k and1,000k M-MSC (n=10, respectively) Diabetes mellitus (DM) was induced by intraperitoneal injection of streptozotocin (STZ) (50 mg/kg) after overnight fasting. Rats with serum glucose over 200mg/dL on day 3 were included. Three weeks after DM induction, different doses of M-MSCS or phosphate buffer solution were directly injected into the submucosal layer at anterior wall or dome of the bladder with 26-gauge needle. One week after injection, awake cystometry, histological and gene expression analysis was performed. Efficacy of 500k M-MSCs (minimum therapeutic dosage) was compared with umbilical cord-derived stem cells (UC-MSC) (n=5) serially at 1, 2, and 4 weeks by awake cystometry.

Results
A single local transplantation of M-MSCs ameliorated DM-induced DUA voiding profiles and bladder histology. Immunostaining and gene expression analysis revealed that the transplanted M-MSCs supported myogenic restoration primarily by engrafting into bladder tissue via pericytes, and subsequently exerting paracrine effects to prevent apoptotic cell death in bladder tissue. The therapeutic efficacy of M-MSCs was superior to that of human umbilical cord-derived MSCs at the early time point (1 week). However, the differences in efficacy between M-MSCs and UC-MSCs were insignificant on long-term follow-up.

Conclusions
Transplantation of M-MSCs into the bladders of DM animals alleviated DUA by integrating into pericytes, providing a favourable microenvironment for myogenic restoration in the DM rat model with detrusor muscle atrophy. In addition, M-MSCs more effectively restored bladder function than currently available MSC therapy. However, duration of the therapeutic effect of M-MSC transplantation was short-term, limited to less than 2 weeks.
keywords : Detrusor underactivity, diabetes mellitus, mesenchymal stem cell

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