Human liver organoids: From generation to applications

Export Generation and application of liver organoids in human disease modeling, drug development and therapeutics. BME, basement membrane-like matrix; CLC, cholangiocyte-like cell; HLC, hepatocyte-like cell; HOs, hepatic organoids; iCOs, intrahepatic cholangiocyte organoids; iPSC; induced pluripotent stem cell; KCL, Kupffer-like cell; ULA, ultra-low attachment. This figure was created using BioRender. 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 liver tissue or pluripotent stem cells generated from 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 are likely to be solved, enabeling 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.