Liver Organoids: Formation Strategies and Biomedical Applications.

The liver is the most important digestive organ in the body. Several studies have explored liver biology and diseases related to the liver. However, most of these studies have only explored liver development, mechanism of liver regeneration and pathophysiology of liver diseases mainly based on two-dimensional (2D) cell lines and animal models. Traditional 2D cell lines do not represent the complex three-dimensional tissue architecture whereas animal models are limited by inter-species differences. These shortcomings limit understanding of liver biology and diseases. Liver organoid technology is effective in elucidating structural and physiological characteristics and basic tissue-level functions of liver tissue. In this review, formation strategies and a wide range of applications in biomedicine of liver organoid are summarized. Liver organoids are derived from single type cell culture, such as induced pluripotent stem cells (iPSCs), adult stem cells, primary hepatocytes, and primary cholangiocytes and multi-type cells co-culture, such as iPSC-derived hepatic endoderm cells co-cultured with mesenchymal stem cells and umbilical cord-derived endothelial cells. In vitro studies report that liver organoids are a promising model for regenerative medicine, organogenesis, liver regeneration, disease modelling, drug screening and personalized treatment. Liver organoids are a promising in vitro model for basic research and for development of clinical therapeutic interventions for hepatopathy.