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首页> 外文期刊>Cell and Tissue Research >Transdifferentiation of human adipose-derived stem cells into urothelial cells: potential for urinary tract tissue engineering
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Transdifferentiation of human adipose-derived stem cells into urothelial cells: potential for urinary tract tissue engineering

机译：人脂肪来源的干细胞转分化为尿道上皮细胞：尿路组织工程的潜力

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Autologous urothelial cells (UCs) provide a cell source for urinary tissue engineering because they can be used safely due to their lack of immunogenicity. However, these cells cannot be harvested under the following circumstances: malignancy, infection and organ loss, etc. Human adipose-derived stem cells (HADSCs) possess the traits of high differentiation potential and ease of isolation, representing a promising resource for tissue engineering and regenerative medicine. Nevertheless, HADSCs have been poorly investigated in urology and the optimal approaches to induce HADSCs into urothelium are still under investigation. In this study, we hypothesized that the change of microenvironment by a conditioned medium was essential for the transdifferentiation of HADSCs into UCs. We then used a conditioned medium derived from urothelium to alternate the microenvironment of HADSCs. After 14 days of culture in a conditioned medium, about 25–50% HADSCs changed their morphology into polygonal epithelium-like shapes. In addition, these cells expressed up-regulating of urothelial lineage-specific markers (uroplakin 2and cytokeratin-18) and down-regulating of mesenchymal marker (vimentin) in RNA and protein level, respectively, which confirmed that HADSCs were induced into urothelial lineage cells. We also measured the growth factors in the conditioned medium in order to analyze the molecular mechanisms regulating transdifferentiation. We observed that the expression levels of PDGF-BB and VEGF were significantly higher than those of the control group after 14 days induction, suggesting they were abundantly secreted into the medium during the culturing period. In conclusion, HADSCs showed in vitro the upregulation of markers for differentiation towards urothelial cells by culturing in an urothelial-conditioned medium, which provides an alternative cell source for potential use in urinary tract tissue engineering.
机译：自体尿路上皮细胞（UCs）为泌尿组织工程学提供了细胞来源，因为它们缺乏免疫原性，因此可以安全使用。但是，在以下情况下无法收获这些细胞：恶性肿瘤，感染和器官丧失等。人脂肪来源的干细胞（HADSC）具有高度分化的潜力和易于分离的特点，代表了组织工程和生物医学的有希望的资源。再生医学。然而，HADSC在泌尿科方面的研究很少，并且仍在研究诱导HADSC进入尿道上皮的最佳方法。在这项研究中，我们假设条件培养基的微环境变化对于HADSCs向UCs的转分化至关重要。然后，我们使用衍生自尿路上皮的条件培养基来替代HADSC的微环境。在条件培养基中培养14天后，约25–50％的HADSC将其形态改变为多边形上皮样形状。另外，这些细胞在RNA和蛋白质水平上分别表达上皮细胞系特异性标记物（uroplakin 2和cytokeratin-18）的上调和间质标记物（波形蛋白）的下调，这证实了HADSC被诱导为上皮细胞系细胞。 。我们还测量了条件培养基中的生长因子，以分析调节转分化的分子机制。我们观察到，PDGF-BB和VEGF的表达水平在诱导14天后显着高于对照组，这表明它们在培养期间大量分泌到培养基中。总之，HADSCs通过在尿路上皮条件培养基中培养，体外显示了向尿路上皮细胞分化的标志物的上调，这为尿路组织工程中的潜在用途提供了另一种细胞来源。

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