Department of Urology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Int J Urol. 2010 Apr;17(4):359-68. doi: 10.1111/j.1442-2042.2010.02471.x. Epub 2010 Feb 25.
To evaluate the functional and histological recovery by autologous bone-marrow-derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters.
BMSC were harvested from female Sprague-Dawley retired breeder rats for later transplantation. The cells were cultured, and transfected with the green fluorescence protein gene. The urethral sphincters were injured by combined urethrolysis and cardiotoxin injection. One week after injury, the cultured BMSC were injected autologously into the periurethral tissues. Controls included sham-operated rats and injured rats injected with cell-free medium (CFM). Abdominal leak point pressures (LPP) were measured before and after surgery during the following 13 weeks. The urethras were then retrieved for histological evaluation. The presence of green-fluorescence-protein-labeled cells and the regeneration of skeletal muscles, smooth muscles, and peripheral nerves were evaluated by immunohistochemical staining.
LPP was significantly reduced in the injured rats. It increased gradually after transplantation, but there was no significant difference between the BMSC and CFM groups. In the BMSC group, transplanted cells survived and differentiated into striated muscle cells and peripheral nerve cells. The proportions of skeletal muscle cells and peripheral nerves in the urethra were significantly greater in the BMSC group compared to the CFM group.
Despite a clear trend towards recovery of LPP in BMSC-transplanted urethras, no significant effect was detected. Further study is required for clinical applications for the treatment of stress urinary incontinence.
评估自体骨髓间充质干细胞(BMSC)移植入损伤大鼠尿道括约肌后的功能和组织学恢复情况。
从雌性 Sprague-Dawley 退休繁殖大鼠中提取 BMSC,用于后续移植。对细胞进行培养,并转染绿色荧光蛋白基因。通过尿道松解和心脏毒素注射联合损伤尿道括约肌。损伤后 1 周,将培养的 BMSC 自体注射到尿道周围组织中。对照组包括假手术大鼠和注射无细胞培养基(CFM)的损伤大鼠。在接下来的 13 周内,在手术前后测量腹压漏点压力(LPP)。然后取出尿道进行组织学评估。通过免疫组织化学染色评估绿色荧光蛋白标记细胞的存在以及骨骼肌、平滑肌和周围神经的再生情况。
损伤大鼠的 LPP 显著降低。移植后逐渐增加,但 BMSC 组和 CFM 组之间无显著差异。在 BMSC 组中,移植的细胞存活并分化为横纹肌细胞和周围神经细胞。与 CFM 组相比,BMSC 组尿道中骨骼肌细胞和周围神经的比例显著增加。
尽管 BMSC 移植尿道的 LPP 有明显的恢复趋势,但未检测到显著效果。需要进一步研究以将其应用于治疗压力性尿失禁的临床治疗。