Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Portugal.
Center for Molecular Medicine, University Medical Center Utrecht and Utrecht University, The Netherlands.
Hepatology. 2024 Jun 1;79(6):1432-1451. doi: 10.1097/HEP.0000000000000343. Epub 2023 Feb 27.
In the last decade, research into human hepatology has been revolutionized by the development of mini human livers in a dish. These liver organoids are formed by self-organizing stem cells and resemble their native counterparts in cellular content, multicellular architecture, and functional features. Liver organoids can be derived from the liver tissue or pluripotent stem cells generated from a skin biopsy, blood cells, or renal epithelial cells present in urine. With the development of liver organoids, a large part of previous hurdles in modeling the human liver is likely to be solved, enabling possibilities to better model liver disease, improve (personalized) drug testing, and advance bioengineering options. In this review, we address strategies to generate and use organoids in human liver disease modeling, followed by a discussion of their potential application in drug development and therapeutics, as well as their strengths and limitations.
在过去的十年中,通过在培养皿中生成迷你人类肝脏,对人类肝脏的研究发生了革命性的变化。这些肝类器官由自我组织的干细胞形成,在细胞成分、多细胞结构和功能特征上与它们的天然对应物相似。肝类器官可以从肝组织或多能干细胞中衍生出来,这些多能干细胞是从皮肤活检、血液细胞或尿液中的肾上皮细胞中产生的。随着肝类器官的发展,在模拟人类肝脏方面的大部分先前障碍很可能会得到解决,从而使我们能够更好地模拟肝脏疾病、改进(个性化)药物测试并推进生物工程选择。在这篇综述中,我们讨论了生成和使用肝类器官来进行人类肝脏疾病建模的策略,然后讨论了它们在药物开发和治疗方面的潜在应用,以及它们的优缺点。