In Vivo and In Vitro Models to Study Liver Fibrosis: Mechanisms and Limitations

Abstract

Because the development and progression of liver fibrosis differ based on the etiology, it is important to select an appropriate liver fibrosis model according to the purpose of study and type of disease. To study liver fibrosis, many in vivo animal and in vitro models have been developed. This review summarizes and analyzes the various in vivo and in vitro liver fibrosis models and their implications and limitations. Liver fibrosis is a common result of liver injury owing to various kinds of chronic liver diseases. A deeper understanding of the pathophysiology of liver fibrosis and identifying potential therapeutic targets of liver fibrosis is important because liver fibrosis may progress to advanced liver diseases, such as cirrhosis and hepatocellular carcinoma. Despite numerous studies, the underlying mechanisms of liver fibrosis remain unclear. Mechanisms of the development and progression of liver fibrosis differ according to etiologies. Therefore, appropriate liver fibrosis models should be selected according to the purpose of the study and the type of underlying disease. Many in vivo animal and in vitro models have been developed to study liver fibrosis. However, there are no perfect preclinical models for liver fibrosis. In this review, we summarize the current in vivo and in vitro models for studying liver fibrosis and highlight emerging in vitro models, including organoids and liver-on-a-chip models. In addition, we discuss the mechanisms and limitations of each model.