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首页> 外文期刊>Cell and Tissue Research >Engineering kidney cells: reprogramming and directed differentiation to renal tissues
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Engineering kidney cells: reprogramming and directed differentiation to renal tissues

机译：工程肾细胞：对肾组织的重新编程和指向分化

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Growing knowledge of how cell identity is determined at the molecular level has enabled the generation of diverse tissue types, including renal cells from pluripotent or somatic cells. Recently, several in vitro protocols involving either directed differentiation or transcription-factor-based reprogramming to kidney cells have been established. Embryonic stem cells or induced pluripotent stem cells can be guided towards a kidney fate by exposing them to combinations of growth factors or small molecules. Here, renal development is recapitulated in vitro resulting in kidney cells or organoids that show striking similarities to mammalian embryonic nephrons. In addition, culture conditions are also defined that allow the expansion of renal progenitor cells in vitro. Another route towards the generation of kidney cells is direct reprogramming. Key transcription factors are used to directly impose renal cell identity on somatic cells, thus circumventing the pluripotent stage. This complementary approach to stem-cell-based differentiation has been demonstrated to generate renal tubule cells and nephron progenitors. In-vitro-generated renal cells offer new opportunities for modelling inherited and acquired renal diseases on a patient-specific genetic background. These cells represent a potential source for developing novel models for kidney diseases, drug screening and nephrotoxicity testing and might represent the first steps towards kidney cell replacement therapies. In this review, we summarize current approaches for the generation of renal cells in vitro and discuss the advantages of each approach and their potential applications.
机译：日益增长的知识在分子水平确定如何确定细胞身份，使得产生不同的组织类型，包括来自多能或体细胞的肾细胞。最近，已经建立了几种涉及定向分化或转录基于转录的重组的体外方案对肾细胞进行了重新编程。通过将它们暴露于生长因子或小分子的组合，可以将胚胎干细胞或诱导的多能干细胞引导朝向肾命运。在这里，肾脏发展在体外重新携带，导致肾细胞或有机体，其显示与哺乳动物胚胎肾脏的醒目相似。此外，还定义了培养条件，其允许在体外扩增肾祖细胞。致肾细胞产生的另一种途径是直接的重编程。键转录因子用于直接对体细胞施加肾细胞同一性，从而绕过多能阶段。已经证明了这种互补的抗细胞分化的分化方法以产生肾小管细胞和肾祖祖细胞。体外生成的肾细胞为患者特异性遗传背景上的遗传和获得肾病的建模提供了新的机会。这些细胞代表了开发肾病，药物筛选和肾毒性测试的新型模型的潜在来源，并且可能代表肾细胞更换疗法的第一步。在本综述中，我们总结了在体外产生肾细胞的电流方法，并讨论了每种方法及其潜在应用的优势。

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