Reconstruction of radical prostatectomy-induced urethral damage using skeletal muscle-derived multipotent stem cells

Reconstruction of radical prostatectomy-induced urethral damage using skeletal muscle-derived multipotent stem cells
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DOI:
10.1097/tp.0b013e318170572b
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发表时间:
2008-06-15
期刊:
影响因子:
6.2
通讯作者:
Terachi, Toshiro
Terachi, Toshiro
中科院分区:
医学2区
文献类型:
--
作者:
Hoshi, Akio;Tamaki, Tetsuro;Terachi, Toshiro

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背景尿道横纹括约肌(URS)和神经血管束(NVB)损伤是根治性尿道切除术的主要并发症。一般认为是由于不可避免的手术对尿道周围的肌肉-神经-血管单位造成的损伤。我们试图用骨骼肌来源的干细胞来治疗这种损伤,这种干细胞能够重建肌肉-神经-血管单位。从绿色荧光蛋白、转基因小鼠和大鼠中酶促提取细胞并通过流式细胞术分选为CD 34(+)/45(-)(Sk-34)和CD 34(-)/45(-)(Sk-DN)细胞。在野生型Sprague-Dawley大鼠和结鼠中,通过手动去除总URS的三分之一和NVB的单侧侵袭来诱导URS-NVB损伤。将新鲜分离的Sk-34、Sk-34+Sk-DN细胞和培养的Sk-DN细胞直接移植到损伤部位。在移植后4周和12周,通过骶骨表面(L 6-S1)电刺激的尿道压力曲线被评价为功能恢复。对照组和移植组4周时的恢复率分别为37.6%和72.9%,12周时分别为41.6%和78.4%(P
Background. Postoperative damage of the urethral rhabdosphincter (URS) and neurovascular bundle (NVB) is a major operative complication of radical prostatectomy. It is generally recognized to be caused by-unavoidable surgical damage to the muscle-nerve-blood vessel units around the urethra. We attempted to treat this damage using skeletal muscle-derived stem cells, which are able to reconstitute muscle-nerve-blood vessel units.Methods. Cells were enzymatically extracted and sorted by flow cytometry as CD34(+)/45(-)(Sk-34) and CD34(-)/45(-)(Sk-DN) cells from green fluorescent protein, transgenic mice and rats. URS-NVB damage was induced by manually removing one-third of the total URS and unilateral invasion of NVB in wild-type Sprague-Dawley and node rats. Freshly isolated Sk-34, Sk-34+Sk-DN cells, and cultured Sk-DN cells were directly transplanted into the damaged portion.Results. At 4 and 12 weeks after transplantation, urethral pressure profile by electrical stimulation through the sacral surface (L6-S1) was evaluated as functional recovery. The recovery ratio in the control and transplanted groups was 37.6% and 72.9%, at 4 weeks, and 41.6% and 78.4% at 12 weeks, respectively (P