1 Department of Urology, University Medical Centre Utrecht , Utrecht, The Netherlands .
2 Regenerative Medicine Center Utrecht , Utrecht, The Netherlands .
Tissue Eng Part B Rev. 2017 Jun;23(3):257-267. doi: 10.1089/ten.TEB.2016.0352. Epub 2016 Dec 2.
Tissue-engineered (TE) urethra is desirable in men with urethral disease (stricture or hypospadias) and shortage of local tissue. Although ideally a TE graft would contain urethral epithelium cells, currently, bladder epithelium (urothelium) is widely used, but morphologically different. Understanding the differences and similarities of urothelium and urethral epithelium could help design a protocol for in vitro generation of urethral epithelium to be used in TE grafts for the urethra.
To understand the development toward urethral epithelium or urothelium to improve TE of the urethra.
A literature search was done following PRISMA guidelines. Articles describing urethral epithelium and bladder urothelium development in laboratory animals and humans were selected.
Twenty-nine studies on development of urethral epithelium and 29 studies on development of urothelium were included. Both tissue linings derive from endoderm and although adult urothelium and urethral epithelium are characterized by different gene expression profiles, the signaling pathways underlying their development are similar, including Shh, BMP, Wnt, and FGF. The progenitor of the urothelium and the urethral epithelium is the early fetal urogenital sinus (UGS). The urethral plate and the urothelium are both formed from the p63+ cells of the UGS. Keratin 20 and uroplakins are exclusively expressed in urothelium, not in the urethral epithelium. Further research has to be done on unique markers for the urethral epithelium.
This review has summarized the current knowledge about embryonic development of urothelium versus urethral epithelium and especially focuses on the influencing factors that are potentially specific for the eventual morphological differences of both cell linings, to be a basis for developmental or tissue engineering of urethral tissue.
组织工程（TE）尿道在患有尿道疾病（狭窄或尿道下裂）和局部组织短缺的男性中是理想的选择。尽管理想情况下，TE 移植物应包含尿道上皮细胞，但目前广泛使用的是膀胱上皮（尿路上皮），但其形态不同。了解尿路上皮和尿道上皮的差异和相似之处有助于设计用于 TE 移植物的尿道上皮体外生成方案。
了解向尿道上皮或尿路上皮的发展，以改善尿道的 TE。
按照 PRISMA 指南进行文献检索。选择描述实验室动物和人类尿道上皮和膀胱尿路上皮发育的文章。
共纳入 29 项关于尿道上皮发育的研究和 29 项关于尿路上皮发育的研究。两种组织衬里均源自内胚层，尽管成人尿路上皮和尿道上皮的基因表达谱不同，但它们的发育所涉及的信号通路相似，包括 Shh、BMP、Wnt 和 FGF。尿路上皮和尿道上皮的祖先是早期胎儿尿生殖窦（UGS）。尿道板和尿路上皮均由 UGS 的 p63+细胞形成。角蛋白 20 和尿 plakins 仅在尿路上皮中表达，不在尿道上皮中表达。需要进一步研究尿道上皮的独特标记物。
本综述总结了目前关于尿路上皮与尿道上皮胚胎发育的知识，特别是重点关注了潜在影响这两种细胞衬里最终形态差异的因素，为尿道组织的发育或组织工程学提供了基础。
