Knuppe Molecular Urology Laboratory, Department of Urology, University of California-San Francisco, San Francisco, California 94143-0738, USA.
J Urol. 2010 Mar;183(3):1232-40. doi: 10.1016/j.juro.2009.11.012. Epub 2010 Jan 22.
Adipose tissue derived stem cells can differentiate into muscle and neuron-like cells in vitro. We investigate the usefulness of adipose tissue derived stem cells for overactive bladder in obese hyperlipidemic rats.
Hyperlipidemia was induced in healthy rats by a high fat diet. The resulting obese hyperlipidemic rats were treated with bladder injection of saline, adipose tissue derived stem cells or tail vein injection of adipose tissue derived stem cells. Bladder function was assessed by 24-hour voiding behavior study and conscious cystometry. Bladder histology was assessed using immunostaining and trichrome staining, followed by image analysis.
Serum total cholesterol and low density lipoprotein were significantly higher in obese hyperlipidemic rats than in normal rats (p <0.01). The micturition interval was shorter in saline treated obese hyperlipidemic rats than in normal rats, obese hyperlipidemic rats that received adipose tissue derived stem cells via the tail vein and obese hyperlipidemic rats that received adipose tissue derived stem cells by bladder injection (mean +/- SEM 143 +/- 28.7 vs 407 +/- 77.9, 281 +/- 43.9 and 368 +/- 66.7 seconds, respectively, p = 0.0084). Bladder wall smooth muscle content was significantly lower in obese hyperlipidemic rats than in normal animals (p = 0.0061) while there was no significant difference between obese hyperlipidemic groups. Nerve content and blood vessel density were lower in controls than in obese hyperlipidemic rats treated with adipose tissue derived stem cells.
Hyperlipidemia is associated with increased urinary frequency, and decreased bladder blood vessel and nerve density in rats. Adipose tissue derived stem cell treatment ameliorates these adverse effects and holds promise as a potential new therapy for overactive bladder.
脂肪组织来源的干细胞可以在体外分化为肌肉和神经元样细胞。我们研究了脂肪组织来源的干细胞在肥胖高脂血症大鼠逼尿肌过度活动中的应用价值。
通过高脂肪饮食诱导健康大鼠产生高脂血症,然后用生理盐水、脂肪组织来源的干细胞或脂肪组织来源的干细胞尾静脉注射处理肥胖高脂血症大鼠。通过 24 小时排尿行为研究和清醒膀胱测压评估膀胱功能。通过免疫染色和三染色进行膀胱组织学评估,然后进行图像分析。
肥胖高脂血症大鼠的血清总胆固醇和低密度脂蛋白明显高于正常大鼠(p<0.01)。与正常大鼠相比,生理盐水处理的肥胖高脂血症大鼠的排尿间隔更短,经尾静脉注射脂肪组织来源的干细胞和膀胱注射脂肪组织来源的干细胞的肥胖高脂血症大鼠的排尿间隔也更短(平均 +/- SEM 143 +/- 28.7 比 407 +/- 77.9、281 +/- 43.9 和 368 +/- 66.7 秒,p=0.0084)。与正常动物相比,肥胖高脂血症大鼠的膀胱壁平滑肌含量明显降低(p=0.0061),而肥胖高脂血症组之间无明显差异。与肥胖高脂血症大鼠相比,脂肪组织来源的干细胞治疗组的神经含量和血管密度较低。
高脂血症与大鼠排尿频率增加以及膀胱血管和神经密度降低有关。脂肪组织来源的干细胞治疗可改善这些不良反应,有望成为治疗逼尿肌过度活动的新方法。