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间质干细胞注射至失代偿兔膀胱后的组织病理学、药理学和尿动力学结果。

The histopathologic, pharmacologic and urodynamic results of mesenchymal stem cell's injection into the decompensated rabbit's bladder.

机构信息

Department of Urology, Gulhane Military Medical Academy, Etlik, 06010 Ankara, Turkey.

出版信息

Stem Cell Rev Rep. 2012 Dec;8(4):1245-53. doi: 10.1007/s12015-012-9393-4.

DOI:10.1007/s12015-012-9393-4
PMID:22736388
Abstract

OBJECTIVES

We researched the survival of bone marrow-derived mesenchymal stem cells (MSCs) and the results of MSCs' injected into decompensated bladders in a rabbit model.

METHODS

Partial bladder neck obstruction (PBNO) and subsequent decompensation of the bladder was achieved by wrapping the bladder neck with autologous rectus fascia. In the first aspect of the experiment 18 rabbits underwent MSC injection into the decompensated bladder to prove the survivability of injected MSCs. For this purpose MSCs were isolated, transfected with Green Fluorescent Protein (GFP), and injected into the detrusor layer. Once viability was assessed in the first phase, an additional 10 rabbits underwent PBNO in the second phase. Five of these animals underwent subsequent MSC injection (group 3, stem cell) and 5 did not (group 2, obstruction). Both groups were compared to 5 controls (group 1). Urodynamics were performed in all groups. After the animals were sacrificed the groups were compared via morphometric analysis, contractile response to carbachol and KCl, and muscarinic receptor type analysis.

RESULTS

On morphometric analysis, collagenous area rates were 43, 53 and 37% in group 1, 2 and 3, respectively. There was no statistically significant difference between groups in terms of bladder weight, bladder capacity and vesical pressure. The contractile effects of KCl and muscarinic agonist carbachol were significantly higher in groups 1 and 3 than group 2. The response to carbachol was antagonized by muscarinic M(1) and M(3) receptor antagonist pirenzepine and abolished by muscarinic M(3) receptor antagonist 4-DAMP in all groups.

CONCLUSIONS

The injection of MSCs decreased the collagenous area, increased detrusor contractility. Functional M(3) receptors were also expressed in MSCs-injected bladder smooth muscle as well as in control group.

摘要

目的

我们研究了骨髓间充质干细胞(MSCs)在兔模型中植入失代偿性膀胱的存活情况和结果。

方法

通过自体腹直肌筋膜包裹膀胱颈部,实现部分膀胱颈部梗阻(PBNO)和随后的膀胱失代偿。在实验的第一部分,18 只兔子接受了 MSC 注射到失代偿性膀胱,以证明注射的 MSC 的存活率。为此,我们分离了 MSC,转染了绿色荧光蛋白(GFP),并将其注射到逼尿肌层。一旦在第一阶段评估了细胞活力,在第二阶段,另外 10 只兔子接受了 PBNO。其中 5 只接受了随后的 MSC 注射(干细胞组,第 3 组),5 只没有(梗阻组,第 2 组)。这两组与 5 只对照组(第 1 组)进行比较。所有组都进行了尿动力学检查。动物死后,通过形态计量学分析、对卡巴胆碱和 KCl 的收缩反应以及毒蕈碱受体类型分析对各组进行比较。

结果

在形态计量学分析中,第 1、2 和 3 组的胶原面积率分别为 43%、53%和 37%。各组之间的膀胱重量、膀胱容量和膀胱压无统计学差异。KCl 和毒蕈碱激动剂卡巴胆碱的收缩效应在第 1 组和第 3 组明显高于第 2 组。各组中,卡巴胆碱的反应均被毒蕈碱 M(1)和 M(3)受体拮抗剂哌仑西平和毒蕈碱 M(3)受体拮抗剂 4-DAMP 拮抗,并被消除。

结论

MSC 注射减少了胶原面积,增加了逼尿肌收缩性。在 MSC 注射的膀胱平滑肌和对照组中也表达了功能性 M(3)受体。

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