Establishment of a 3D hyperuricemia model based on cultured human liver organoids

Abstract

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.

Keywords: Disease model; Human liver organoids; Hyperuricemia; Uric acid.