Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells.
Advancements in Disease Modeling and Drug Discovery Using iPSC-Derived Hepatocyte-like Cells.
复制标题
使用IPSC衍生的肝细胞样细胞发现疾病建模和药物发现的进步。
DOI：
10.3390/genes13040573
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发表时间：
2022-03-24
期刊：
影响因子：
3.5
通讯作者：
Duncan, Stephen A.
中科院分区：
文献类型：
--
作者：
Blaszkiewicz, Josef;Duncan, Stephen A.
作为人体的代谢中心，肝脏是执行各种重要生理功能的重要器官。虽然以其再生潜力而闻名，但它仍然容易受到各种疾病的影响。尽管经过数十年的研究，肝病仍然是美国死亡的主要原因，每年造成数十亿美元的经济负担。先前对模型系统的研究，如原代肝细胞和小鼠模型，已经提供了许多重要的发现。然而，与这些模式有关的许多障碍阻碍了进展。近年来，基于诱导多能干细胞（iPSC）的系统已成为研究肝脏疾病的有利平台。这些优点，包括保留的分化和生理功能，通过CRISPR/Cas9等工具进行遗传操作的适应性，以及高通量筛选的可用性，使这些系统对疾病的机制研究和新疗法的鉴定越来越有吸引力。虽然存在局限性，但最近的研究在改善这些问题方面取得了进展。在这篇综述中，我们讨论了基于iPSC的肝病模型的最新进展，包括模型系统构建的改进以及高通量筛选在遗传研究和药物发现中的应用。
Serving as the metabolic hub of the human body, the liver is a vital organ that performs a variety of important physiological functions. Although known for its regenerative potential, it remains vulnerable to a variety of diseases. Despite decades of research, liver disease remains a leading cause of mortality in the United States with a multibillion-dollar-per-year economic burden. Prior research with model systems, such as primary hepatocytes and murine models, has provided many important discoveries. However, progress has been impaired by numerous obstacles associated with these models. In recent years, induced pluripotent stem cell (iPSC)-based systems have emerged as advantageous platforms for studying liver disease. Benefits, including preserved differentiation and physiological function, amenability to genetic manipulation via tools such as CRISPR/Cas9, and availability for high-throughput screening, make these systems increasingly attractive for both mechanistic studies of disease and the identification of novel therapeutics. Although limitations exist, recent studies have made progress in ameliorating these issues. In this review, we discuss recent advancements in iPSC-based models of liver disease, including improvements in model system construction as well as the use of high-throughput screens for genetic studies and drug discovery.
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