Periurethral Injection of Autologous Adipose-Derived Stem Cells with Controlled-Release Nerve Growth Factor for the Treatment of Stress Urinary Incontinence in a Rat Model
Periurethral Injection of Autologous Adipose-Derived Stem Cells with Controlled-Release Nerve Growth Factor for the Treatment of Stress Urinary Incontinence in a Rat Model
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DOI：
10.1016/j.eururo.2010.10.038
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发表时间：
2011-01-01
期刊：
影响因子：
23.4
通讯作者：
Xiu, Youcheng
中科院分区：
文献类型：
--
作者：
Zhao, Weiming;Zhang, Cheng;Xiu, Youcheng
背景：干细胞疗法是治疗压力性尿失禁（SUI）的一种很有前途的治疗策略。目的：设计一种含有自体脂肪干细胞（ADSC）和神经生长因子（NGF）控释的干细胞移植系统。我们评估了这个系统是否可以提高治疗效果的ADSCs通过尿道周围coinjection在SUI rats.Design，设置，和participants：我们首先测试了大鼠ADSCs中的神经生长因子受体的存在，并观察在体外和体内的ADSCs的神经生长因子的影响。将神经生长因子包裹在聚乳酸-羟基乙酸-PLGA微球（PLGA/NGF）中以控制其释放。在大鼠中产生SUI，并收获ADSC，从脂肪组织中培养，并保留用于以后的移植。SUI大鼠接受不同形式的尿道周围注射治疗。监测尿动力学指标。干预：将40只SUI大鼠随机分为5组，每组10只，分别在尿道周围注射磷酸盐缓冲液（PBS）、ADSC、ADSC + PLGA、ADSC + NGF、ADSC + PLGA/NGF。膀胱容量，腹部漏尿点压力（ALPP），和逆行尿道灌注压（RUPP）在2，6，和8 wk后injection.Measurements：大鼠SUI模型产生的双侧阴部神经横断（PNT）。实时荧光定量聚合酶链反应（RT-PCR）和蛋白质印迹法检测NGF受体Ark-A。肌肉和周围神经的再生进行了评估，通过Masson的三色和免疫组化staining.Results和局限性：结果显示，存在的NGF受体Trk-A对大鼠ADSCs。短期观察表明，NGF能提高ADSCs在体内外的存活率。ADSC与PLGA/NGF组合肌内递送到尿道中导致ALPP和RUPP以及肌肉和神经节的量的显著改善。ADSC + PLGA/NGF组与其他组比较差异有统计学意义。结论：尿道周围联合注射自体ADSC和控释NGF可能是治疗SUI的一种潜在策略。(C)2010年欧洲泌尿外科协会。Elsevier B. V.出版，保留所有权利。
Background: Stem cell therapy is a promising therapeutic strategy for stress urinary incontinence (SUI). However, its current efficacy is insufficient.Objective: We designed a stem cell transplantation system that contains autologous adipose-derived stem cells (ADSC) and controlled-release nerve growth factor (NGF). We evaluated whether this system could enhance the therapeutic efficacy of ADSCs by periurethral coinjection in SUI rats.Design, setting, and participants: We first tested for the presence of NGF receptors in rat ADSCs and observed the effect of NGF on ADSCs in vitro and in vivo. NGF was encapsulated within poly(lactic-coglycolic acid-PLGA) microspheres (PLGA/NGF) to control its release. SUI was created in rats, and ADSCs were harvested, cultured from fat tissue, and retained for later transplantation. SUI rats then received different forms of periurethral injection therapy. Their urodynamic index was monitored. Eight weeks after injection, the SUI rats were sacrificed and their urethra removed for histologic evaluation.Intervention: Forty SUI rats were allocated to five groups for receiving periurethral injection with phosphate-buffered saline (PBS), ADSC, ADSC + PLGA, ADSC + NGF, or ADSC + PLGA/NGF. Bladder capacities, abdominal leak point pressure (ALPP), and retrograde urethral perfusion pressure (RUPP) were reassessed at 2, 6, and 8 wk after injection.Measurements: The rat SUI model was generated by bilateral pudendal nerve transection (PNT). Real-time polymerase chain reaction (RT-PCR) and western blotting detected the NGF receptor Ark-A. The regeneration of muscles and peripheral nerves was evaluated by Masson's trichrome and immunohistochemical staining.Results and limitations: Results revealed the presence of the NGF receptor Trk-A on rat ADSCs. Shortterm observations showed that NGF could improve ADSCs' viability in vitro and in vivo. ADSCs delivered intramuscularly into the urethra in combination with PLGA/NGF resulted in significant improvements in ALPP and RUPP as well as the amount of muscle and ganglia. There was a significant difference between the ADSC + PLGA/NGF group and other groups.Conclusions: Periurethral coinjection of autologous ADSCs with controlled-release NGF may be a potential strategy for SUI treatment. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.