Induction of Functional Hepatocyte-Like Cells by Overexpression of FOXA3 and HNF4α in Rat Bone Marrow Mesenchymal Stem Cells.

Liver regeneration has always been of great therapeutic interest, particularly to generate hepatocytes from other types of cells including adult stem cells and induced pluripotent stem cells. In this study, it was found that overexpression of both FOXA3 and HNF4α can convert rat bone marrow mesenchymal stem cells (BMSCs) to functional hepatocyte-like cells (HLCs). The results show that these HLCs had the typical hepatocyte morphology with unique hepatocyte markers such as ALB, G6P, KRT18, TAT, TTR, KRT19 and AFP. Simultaneously, they also exhibited hepatic functions such as glycogen storage, indocyanine green absorption, and cytoplasmic accumulation of neutral triglycerides and lipids. In addition to that, these functions could be maintained in the process of cell culture, thus suggesting that FOXA3 and HNF4α are powerful transcription factors for inducing rat BMSCs to differentiate into functional HLCs, and this study will provide a novel method to generate HLCs.