Dai Keqiang, Chen Ran, Ding Yi, Niu Zhipeng, Fan Jinyu, Xu Cunshuan
State Key Laboratory Cultivation Base for Cell Differentiation Regulation, Henan Normal University, Xinxiang, PR China.
Cells Tissues Organs. 2014;200(2):132-40. doi: 10.1159/000380762. Epub 2015 Apr 16.
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.
肝脏再生一直具有极大的治疗意义，特别是利用包括成体干细胞和诱导多能干细胞在内的其他类型细胞来生成肝细胞。在本研究中，发现FOXA3和HNF4α的过表达可将大鼠骨髓间充质干细胞（BMSC）转化为功能性肝样细胞（HLC）。结果表明，这些HLC具有典型的肝细胞形态，带有诸如ALB、G6P、KRT18、TAT、TTR、KRT19和AFP等独特的肝细胞标志物。同时，它们还表现出肝功能，如糖原储存、吲哚菁绿摄取以及中性甘油三酯和脂质的细胞质积累。除此之外，这些功能在细胞培养过程中能够得以维持，因此表明FOXA3和HNF4α是诱导大鼠BMSC分化为功能性HLC的强大转录因子，并且本研究将提供一种生成HLC的新方法。
