Cell-based therapy is a potential alternative to liver transplantation. The goal of the present study was to examine the in vivo and in vitro hepatic differentiation potential of adipose tissue-derived mesenchymal stem cells (AT-MSCs) and to explore its therapeutic use. AT-MSCs were isolated and cultured with hepatic differentiation medium. Bioactivity assays were used to study the properties of AT-MSCs. The morphology of differentiated AT-MSCs in serum-free hepatic differentiation medium changed into polygonal epithelial cells, while the morphology of AT-MSCs in a similar medium containing 2% fetal bovine serum remained unchanged. The differentiated cells cultured without serum showed hepatocyte-like cell morphology and hepatocyte-specific markers, including albumin (ALB) and α-fetoprotein. The bioactivity assays revealed that hepatocyte-like cells could take up low-density lipoprotein (LDL) and store glycogen. Furthermore, trichostatin A (TSA) enhanced ALB production and LDL uptake by the hepatocyte-like cells, analogous to the functions of human liver cells. ALB was detected in the livers of the CCl4-injured mice one month post-transplantation. This suggested that transplantation of the human AT-MSCs could relieve the impairment of acute CCl4-injured livers in nude mice. This therefore implied that adipose tissue was a source of multipotent stem cells which had the potential to differentiate into mature, transplantable hepatocyte-like cells in vivo and in vitro. In addition, the present study determined that TSA was essential to promoting differentiation of human MSC towards functional hepatocyte-like cells. The relief of liver injury following treatment with AT-MSCs suggested their potential as a novel therapeutic method for liver disorders or injury.
These findings implicated that miR-142 was a tumour suppressor gene in HCC and often hyermethylated to increase TGF-β-induced development of hepatocellular carcinoma.
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