Abstract:
The liver is an essential organ that is involved in the metabolism, synthesis, and secretion of serum proteins and detoxification of xenobiotic compounds and alcohol. Studies on liver diseases have largely relied on cancer-derived cell lines that have proven to be inferior due to the lack of drug-metabolising enzymes. Primary human hepatocytes are considered the gold-standard for evaluating drug metabolism. However, several factors such as lack of donors, high cost of cells, and loss of polarity of the cells have limited their widescale adoption and utility. Stem cells have emerged as an alternative source for liver cells that could be utilised for studying liver diseases, developmental biology, toxicology testing, and regenerative medicine. In this article, we describe in detail an optimised protocol for the generation of multicellular 3D liver organoids composed of hepatocytes, stellate cells, and Kupffer cells as a tractable robust model of the liver. Key features • Optimising a protocol for generating multicellular 3D liver organoids from induced pluripotent stem cells. Graphical overview.
摘要:
肝脏是参与新陈代谢的重要器官,合成,以及血清蛋白的分泌和异生化合物和酒精的解毒。对肝脏疾病的研究很大程度上依赖于癌症来源的细胞系,由于缺乏药物代谢酶,这些细胞系已被证明是劣质的。原代人肝细胞被认为是评估药物代谢的金标准。然而,几个因素,如缺乏捐助者,高成本的细胞,和失去极性的细胞限制了他们的广泛采用和效用。干细胞已成为肝细胞的替代来源,可用于研究肝病,发育生物学,毒理学测试,和再生医学。在这篇文章中,我们详细描述了用于生成由肝细胞组成的多细胞3D肝脏类器官的优化方案,星状细胞,和Kupffer细胞作为肝脏的一个可处理的稳健模型。主要特征•优化从诱导多能干细胞产生多细胞3D肝类器官的方案。图形概述。