Epithelial-Differentiated Adipose-Derived Stem Cells Seeded Bladder Acellular Matrix Grafts for Urethral Reconstruction: An Animal Model

Epithelial-Differentiated Adipose-Derived Stem Cells Seeded Bladder Acellular Matrix Grafts for Urethral Reconstruction: An Animal Model
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用于尿道重建的上皮分化脂肪干细胞接种膀胱脱细胞基质移植物:动物模型

DOI:
10.1089/ten.tea.2013.0122
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发表时间:
2014-02-01
影响因子:
4.1
通讯作者:
Lv, Xiangguo
Lv, Xiangguo
中科院分区:
医学3区
文献类型:
--
作者:
Li, Hongbin;Xu, Yuemin;Lv, Xiangguo

文献摘要

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可用上皮组织的数量有限被认为是尿道重建失败率高的主要原因。本研究的目的是探讨上皮分化兔脂肪源性干细胞(epithelial-differentiated rabbit fat -derived stem cells, epth - rascs)能否在体内功能上发挥上皮蛋白的作用,并成为尿路上皮的潜在替代品。我们使用5-溴-2 ' -脱氧尿苷(BrdU)标记后的epth - rascs植入膀胱脱细胞基质移植物(BAMGs)对雄性新西兰兔进行替代尿道成形术修复前尿道缺损,其基础是我们之前描述的体外上皮诱导系统。用无细胞bamg和未分化的rasc (un - rasc)种子bamg进行尿道成形术作为对照。术后经逆行尿道造影及肉眼观察,epth - rascs /BAMG组移植物挛缩明显改善,尿道连续性恢复。免疫荧光显示brdu标记的epth - rasc / un - rasc与细胞角蛋白13ormyosin共定位。与western blotting结果一致,在植入后早期,epth - rascs /BAMG组上皮细胞呈连续的局部多层结构,而BAMG组和un - rascs /BAMG组上皮细胞未见明显生长和局部单层生长。结果表明,上皮- rasc可作为尿路上皮的潜在替代品用于尿道组织工程,并可用于预防管腔挛缩及其并发症,包括复发性狭窄。
The limited amount of available epithelial tissue is considered a main cause of the high rate of urethral reconstruction failures. The aim of this study was to investigate whether epithelial-differentiated rabbit adipose-derived stem cells (Epith-rASCs) could play a role of epitheliumin vivofunctionally and be a potential substitute of urothelium. Substitution urethroplasty was performed to repair an anterior urethral defect in male New Zealand rabbits using Epith-rASCs seeded bladder acellular matrix grafts (BAMGs) after 5-bromo-2′-deoxyuridine (BrdU) labeling, based on thein vitroepithelial induction system we previously described. Urethroplasty with cell-free BAMGs and with undifferentiated rASCs (Und-rASCs) seeded BAMGs were performed as controls. After surgery, a notable amelioration of graft contracture and recovery of urethral continuity were observed in the Epith-rASCs/BAMG group by retrograde urethrograms and macroscopic inspection. Immunofluorescence revealed that the BrdU-labeled Epith-rASCs/Und-rASCs colocalized withcytokeratin 13ormyosin. Consistent with the results of western blotting, at early postimplantation stage, the continuous epithelial layer with local multilayered structure was observed in the Epith-rASCs/BAMG group, whereas no significant growth and local monolayer growth profile of epithelial cells were observed in the BAMG and Und-rASCs/BAMG group, respectively. The results showed that Epith-rASCs could serve as a potential substitute of urothelium for urethral tissue engineering and be available to prevent lumen contracture and subsequent complications including recurrent stricture.