Autologous bone-marrow-derived mesenchymal stem cell transplantation into injured rat urethral sphincter

Autologous bone-marrow-derived mesenchymal stem cell transplantation into injured rat urethral sphincter
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DOI:
10.1111/j.1442-2042.2010.02471.x
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发表时间:
2010-04-01
影响因子:
2.6
通讯作者:
Nishizawa, Osamu
Nishizawa, Osamu
中科院分区:
医学3区
文献类型:
--
作者:
Kinebuchi, Yoshiaki;Aizawa, Naoki;Nishizawa, Osamu

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目的:探讨自体骨髓间充质干细胞(bone marrow derived mesenchymal stem cells,BMSC)移植修复大鼠尿道括约肌损伤的效果。培养细胞,并用绿色荧光蛋白基因转染。采用尿道松解术联合心脏毒素注射损伤尿道括约肌。伤后1周,将培养的骨髓间充质干细胞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,在手术前后测量腹部漏尿点压力(LPP)。然后取出尿道进行组织学评价。免疫组化染色观察损伤大鼠骨骼肌、平滑肌和周围神经再生情况及绿色荧光蛋白标记细胞的存在。移植后逐渐升高,但骨髓间充质干细胞组与骨髓基质干细胞组间无显著性差异。骨髓间充质干细胞组移植细胞存活,并分化为横纹肌细胞和周围神经细胞。骨骼肌细胞和周围神经在尿道的比例显着更大的BMSC组相比,CFM group.Conclusions:尽管有明显的趋势,在BMSC移植的尿道LPP恢复,没有显着的效果被检测到。压力性尿失禁的临床应用尚需进一步研究。
Objectives:To evaluate the functional and histological recovery by autologous bone-marrow-derived mesenchymal stem cell (BMSC) transplantation into injured rat urethral sphincters.Methods: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.Results: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.Conclusions: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.