Conversion of Fibroblasts to Hepatocyte-Like Cells In Vivo

• Published in: Methods in molecular biology (Clifton, N.J.) Vol. 1905; p. 103
• Main Authors: Song, Guangqi, Yuan, Qinggong, Dai, Zhen, Tsay, Hsin-Chieh, Shen, Xizhong, Ott, Michael, Sharma, Amar Deep
• Format: Journal Article
• Language: English
• Published: United States 2019
• Subjects: Animals; Carbon Tetrachloride - adverse effects; Cell Lineage; Cellular Reprogramming; Dependovirus - genetics; Disease Models, Animal; Fibroblasts - cytology; Fibroblasts - metabolism; GATA4 Transcription Factor - genetics; Genetic Vectors - administration & dosage; Hepatocyte Nuclear Factor 1-alpha - genetics; Hepatocyte Nuclear Factor 3-gamma - genetics; Hepatocyte Nuclear Factor 4 - genetics; Hepatocytes - cytology; Hepatocytes - metabolism; Humans; Liver Cirrhosis - chemically induced; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Liver Cirrhosis - therapy; Mice; Pyridines - adverse effects; Transcription Factors - genetics; In vivo reprogramming; Induced hepatocytes (iHeps)
• ISSN: 1940-6029
• DOI: 10.1007/978-1-4939-8961-4_10

In vivo conversion of fibroblasts into hepatocyte-like cells provides one potential approach for the treatment of liver fibrosis. In our previous study, we showed in vivo conversion of myofibroblasts into induced hepatocytes (iHeps) by forced expression of four transcription factors in genetic fate-tracing mouse model of chronic liver disease. These in vivo-generated iHeps showed similar expression profile with endogenous hepatocytes (eHeps) and also exhibited similar functional characteristics, such as albumin secretion, urea synthesis, cytochrome activity, and drug responsiveness. Furthermore, the targeted expression of our reprogramming factors in myofibroblasts attenuated liver fibrosis. Our study suggests that in vivo reprogramming may open new perspectives for the treatment of diseases such as liver fibrosis.