Hamilton College, 198 College Hill Rd, Clinton, NY 13323, U.S.A.
Cell Biol Int. 2014 Apr;38(4):531-7. doi: 10.1002/cbin.10232. Epub 2014 Jan 13.
Human amniotic fluid stem cells (HAFSCs) have a high proliferative capacity and a good differentiation potential, and may thus be suitable for regenerative medicine. To date, urothelial differentiation mechanisms of HAFSCs are poorly understood. We have investigated the urothelial differentiation potential of HAFSCs so that they can be therapeutically applied to cure defective diseases of bladder. To induce the stem cell differentiation, HAFSCs were cultured in a bladder cancer-derived conditioned medium. After 2 weeks of culture, HAFSCs began to express the urothelial lineage-specific markers (UPII, CK8 and FGF10). Meanwhile, pluripotency markers (Oct-4, Sox-2 and Nanog) were downregulated at both RNA and protein levels in the differentiated HAFSCs. Immunocytochemistry data revealed that differentiated HAFSCs expressed urothelial markers of UPII and CK8. We have screened the receptor tyrosine kinase arrays with the differentiated HAFSCs. The screening showed that MuSK, Tie-1 and EphA4 receptor tyrosine kinases were upregulated, whereas EphA7 and FGF R1 kinases were downregulated in HAFSCs. The data suggest that HAFSCs can be an important urothelium cell source, which can be used for urinary tract engineering.
人羊水干细胞(HAFSCs)具有高增殖能力和良好的分化潜能,因此可能适用于再生医学。迄今为止,HAFSCs 的尿路上皮分化机制还知之甚少。我们研究了 HAFSCs 的尿路上皮分化潜能,以便将其用于治疗膀胱缺陷性疾病的治疗。为了诱导干细胞分化,将 HAFSCs 在膀胱癌衍生的条件培养基中培养。培养 2 周后,HAFSCs 开始表达尿路上皮谱系特异性标志物(UPII、CK8 和 FGF10)。同时,在分化的 HAFSCs 中,多能性标志物(Oct-4、Sox-2 和 Nanog)在 RNA 和蛋白质水平上均下调。免疫细胞化学数据显示,分化的 HAFSCs 表达尿路上皮标志物 UPII 和 CK8。我们用分化的 HAFSCs 对受体酪氨酸激酶阵列进行了筛选。筛选结果表明,MuSK、Tie-1 和 EphA4 受体酪氨酸激酶上调,而 EphA7 和 FGF R1 激酶下调。数据表明,HAFSCs 可以成为重要的尿路上皮细胞来源,可用于尿路工程。