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血小板衍生生长因子-BB 和血管内皮生长因子与膀胱去细胞基质联合应用增强兔模型膀胱扩大中的平滑肌再生和血管生成。

Coadministration of platelet-derived growth factor-BB and vascular endothelial growth factor with bladder acellular matrix enhances smooth muscle regeneration and vascularization for bladder augmentation in a rabbit model.

机构信息

Department of Urology, Nanjing University School of Medicine, Affiliated Drum Tower Hospital, Nanjing, China.

出版信息

Tissue Eng Part A. 2013 Jan;19(1-2):264-76. doi: 10.1089/ten.TEA.2011.0609. Epub 2012 Nov 16.

Abstract

Tissue-engineering techniques have brought a great hope for bladder repair and reconstruction. The crucial requirements of a tissue-engineered bladder are bladder smooth muscle regeneration and vascularization. In this study, partial rabbit bladder (4×5 cm) was removed and replaced with a porcine bladder acellular matrix (BAM) that was equal in size. BAM was incorporated with platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor (VEGF) in the experimental group while with no bioactive factors in the control group. The bladder tissue strip contractility in the experimental rabbits was better than that in the control ones postoperation. Histological evaluation revealed that smooth muscle regeneration and vascularization in the experimental group were significantly improved compared with those in the control group (p<0.05), while multilayered urothelium was formed in both groups. Muscle strip contractility of neobladder in the experimental group exhibited significantly better than that in the control (p<0.05) assessed with electrical field stimulation and carbachol interference. The activity of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the native bladder tissue around tissue-engineered neobladder in the experimental group was significantly higher than that in the control (p<0.05). This work suggests that smooth muscle regeneration and vascularization in tissue-engineered neobladder and recovery of bladder function could be enhanced by PDGF-BB and VEGF incorporated within BAM, which promoted the upregulation of the activity of MMP-2 and MMP-9 of native bladder tissue around the tissue-engineered neobladder.

摘要

组织工程技术为膀胱修复和重建带来了巨大的希望。组织工程膀胱的关键要求是膀胱平滑肌再生和血管化。在这项研究中,部分兔膀胱(4×5cm)被切除并用大小相等的猪膀胱去细胞基质(BAM)替代。实验组 BAM 中加入血小板衍生生长因子-BB(PDGF-BB)和血管内皮生长因子(VEGF),而对照组中则没有生物活性因子。实验组术后兔膀胱组织条的收缩性优于对照组。组织学评估显示,实验组平滑肌再生和血管化明显优于对照组(p<0.05),同时两组均形成多层尿路上皮。实验组新膀胱的肌条收缩性明显优于对照组(p<0.05),这是用电场刺激和卡巴胆碱干扰评估的。实验组组织工程新膀胱周围天然膀胱组织中基质金属蛋白酶-2(MMP-2)和 MMP-9 的活性明显高于对照组(p<0.05)。这项工作表明,PDGF-BB 和 VEGF 掺入 BAM 可增强组织工程新膀胱中的平滑肌再生和血管化以及膀胱功能的恢复,这促进了组织工程新膀胱周围天然膀胱组织中 MMP-2 和 MMP-9 活性的上调。

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