Human embryonic stem cell-derived mesenchymal stem cells have potential of high differentiation into hepatocyte-like cells through increased level of hepatocyte growth factor

Background: As the aging society progresses, more patients are waiting for liver transplantation. However, the function of existing bio artificial liver is insufficient. Recently, research has been focused on stem cells to regenerate damaged liver. Most of all, the obstacle to the commercialization of widely used human adipose tissue-derived stem cells (hASCs) therapy is the limited supply of cells with consistent quality although most cell source of current stem cell therapy is hASCs. In this study, we attempt to differentiate human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) into hepatocyte-like cells and tested whether hESC-MSCs have a potential of liver regeneration as a source of cell therapy, considering that they have characteristics of high differentiation rates, unlimited proliferation possibility from a single colony, and homogenicity.Methods: hESC-MSCs and hASCs were cultured under condition of hepatogenic differentiation in vitro. And then various experiments including quantitative real-time PCR, immunoblotting, ELISA, immunofluorescence, Periodic acid-Schiff staining and flow cytometry analysis were performed to evaluate expression level of HGF and the extent of differentiation into hepatocyte-like cells.Results: We found that hepatocyte growth factor (HGF), important for maintaining hepatocyte activity, is highly expressed in hESC-MSCs. Besides, it was confirmed that the expression of ALB, TDO2, and CYP2E1, which are the hepatocyte-specific genes when hepatogenic differentiation was performed under conditions even without HGF in hESC-MSCs, was higher than that when hASCs was differentiated into hepatocytes. Likewise, we concluded that hESC-MSCs could be well-differentiated into hepatocyte-like cells compared to hASCs through staining data.Conclusions: We propose that hESC-MSCs have a promising potential as a commercial cell therapy source to treat liver failure in view of the limited available cell sources for stem cell therapy.