Hou Chuanli, Hu Yang, Jiang Hong, Xu Zhenzhen, Sha Wanqian, Liu Juncheng, Ren Jiaoyan, Yao Maojin
School of Food Sciences and Engineering, South China University of Technology, Guangzhou, 510641, China.
The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease & China State Key Laboratory of Respiratory Disease, Guangzhou, 510182, China.
Free Radic Biol Med. 2022 Jan;178:7-17. doi: 10.1016/j.freeradbiomed.2021.11.023. Epub 2021 Nov 22.
Hyperuricemia (HUA) is a metabolic disorder caused by abnormal purine metabolism, the prevalence of which has increased worldwide. Here, a 3D organoid culture system for mimicking HUA in vitro was established using cultured human liver organoids. Liver organoids can be generated from single hepatocytes and passaged for several months, retaining key morphological features, functional purine metabolism and global gene expression profile. Furthermore, organoids can be differentiated into hepatocytes with high expression of maturation markers including the hepatocyte nuclear factor-4-alpha (HNF4α), E-cadherin (E-Ca), and albumin (ALB). Importantly, organoids can produce high level of uric acid after xanthine induction which is the substrate of xanthine oxidase. Furthermore, the preclinical application potential of this organoid model was verified by measuring the antihyperuricemic effect of the widely used allopurinol, as well as the reported bioactive substance puerarin. The results demonstrate that this novel organoid model could be used for high-throughput screening of both chemical and food-derived compounds with antihyperuricemic bioactivity.
高尿酸血症（HUA）是一种由嘌呤代谢异常引起的代谢紊乱疾病，其在全球范围内的患病率呈上升趋势。在此，利用培养的人肝脏类器官建立了一种用于在体外模拟HUA的三维类器官培养系统。肝脏类器官可由单个肝细胞生成并传代数月，保留关键的形态特征、功能性嘌呤代谢和整体基因表达谱。此外，类器官可分化为高表达成熟标志物的肝细胞，这些标志物包括肝细胞核因子-4-α（HNF4α）、E-钙黏蛋白（E-Ca）和白蛋白（ALB）。重要的是，在黄嘌呤诱导后，类器官可产生高水平的尿酸，黄嘌呤是黄嘌呤氧化酶的底物。此外，通过测量广泛使用的别嘌醇以及已报道的生物活性物质葛根素的降尿酸作用，验证了该类器官模型的临床前应用潜力。结果表明，这种新型类器官模型可用于高通量筛选具有降尿酸生物活性的化学和食品衍生化合物。
