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经尿道周围注射低血清培养脂肪源性间充质基质细胞增加大鼠尿道阻力。

Increased urethral resistance by periurethral injection of low serum cultured adipose-derived mesenchymal stromal cells in rats.

机构信息

Department of Nephrology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.

出版信息

Int J Urol. 2011 Sep;18(9):659-66. doi: 10.1111/j.1442-2042.2011.02795.x. Epub 2011 Jun 26.

Abstract

OBJECTIVES

To evaluate the effects of a periurethral injection of low serum cultured adipose tissue-derived mesenchymal stromal cells (LASC) and to develop a new autologous cell therapy for stress urinary incontinence.

METHODS

F344 rats were divided into three groups as based on the periurethral injection of LASC, GAX collagen or vehicle (control). At 2 and 4 weeks after injection, leak point pressure (LPP) was measured before and after transection of the pelvic nerves. For cell tracking, LASC of green fluorescent protein transgenic rats were injected into nude rats.

RESULTS

At 2 weeks, both the LASC and collagen groups showed significantly higher LPP than the control group. At 4 weeks, the increase in LPP in the LASC group remained, whereas LPP in the collagen group decreased to baseline levels. In the absence of the urethral closure reflex after transection of the pelvic nerves, LPP in the LASC group was significantly higher than that in the other two groups. Histologically, the size of the urethral lumen was smaller in the LASC group than the collagen group. At 4 weeks, most of the LASC were positive for myogenic antigens including α-smooth muscle actin, desmin and calponin I.

CONCLUSIONS

Periurethral injection of autologous LASC capable of myogenic differentiation made a greater contribution to the increase in urethral resistance than did the conventional collagen bulk injection. Thus, its use for treatment of stress urinary incontinence can be postulated.

摘要

目的

评估尿道周围注射低血清培养脂肪组织源性间充质基质细胞(LASC)的效果,并开发一种新的用于治疗压力性尿失禁的自体细胞疗法。

方法

F344 大鼠根据尿道周围注射 LASC、GAX 胶原或载体(对照)分为三组。在注射后 2 和 4 周,在切断骨盆神经前后测量漏点压(LPP)。为了进行细胞示踪,将绿色荧光蛋白转基因大鼠的 LASC 注射到裸鼠中。

结果

在 2 周时,LASC 和胶原组的 LPP 均明显高于对照组。在 4 周时,LASC 组的 LPP 增加仍然存在,而胶原组的 LPP 下降至基线水平。在切断骨盆神经后尿道闭合反射缺失的情况下,LASC 组的 LPP 明显高于其他两组。组织学上,LASC 组的尿道腔大小小于胶原组。在 4 周时,大多数 LASC 对肌原性抗原(包括α-平滑肌肌动蛋白、结蛋白和钙调蛋白 I)呈阳性。

结论

与传统的胶原块状注射相比,尿道周围注射具有成肌分化能力的自体 LASC 对增加尿道阻力的贡献更大。因此,可以推测其用于治疗压力性尿失禁。

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