Progress, application and challenges of liver organoids

Abstract

The liver, the largest solid organ in the body, is susceptible to metabolic diseases and malignant tumors. Studying its physiological and pathological processes helps to optimize the clinical treatment. Organoids are a novel tool for studying physical development, disease mechanisms, and high-throughput drug screening due to their similarity in composition, structure, and function to internal organs. Recent studies have shown that stem cells, hepatocytes, or cholangiocytes can form “liver organoids” under the synergistic action of specific extracellular matrix and various signaling molecules. This review outlines techniques for generating liver organoids that maximally recapitulate the liver structure and functions in vitro and thoroughly discusses the customary applications of organoids derived from liver tissue, induced pluripotent stem cells (iPSCs) and liver tumors. In this review, a meticulous analysis is provided of the comparatively advanced culture systems used in the construction of liver cancer-derived organoids. Additionally, we reviewed the progress of liver organoids in disease modeling, drug efficacy, and toxicity evaluation, in hopes of generating innovative ideas for the research and applications of liver organoids.

Funding

Natural Science Foundation of Shanghai Municipality,(No. 21JC1401200)