Research on stem cells as candidates to be differentiated into hepatocytes

Liver diseases have become one of the most important causes of morbidity and mortality in the world. Cell therapy and liver transplantation are though to be two treatment options well accepted. However, the shortage of cells sources in cytotherapy and the lack of liver donor in liver transplantation are the major obstacles for the performance of these treatment methods. It urged us to find new origins of extra-hepatic cells. A number of recent studies show that extra-hepatic mesenchymal stem cells (MSC) from different tissues can be differentiated into hepatocytes like cells (HLC). Several hepatic differentiation protocols of MSC have been published in recent years, based on cellular stimulation with exogenous cytokines/growth factors, co-culture with fetal or adult hepatocytes, 2- or 3-dimensional (2D, 3D) matrices to favor differentiation. Independently from the starting stem cells population used, some minimal criteria must be fulfilled to ensure therapeutic success: in vitro expandability, expression of hepatic like surface markers, with hepatic cell functions, and minimal or absent immunogenicity in the recipient host. In this review, we focused on stem cells originated from bone marrow, umbilical cord and adipose tissue which are widely investigated in recent years and have been proved to have liver regenerative potential, the factors used to differentiate stem cells to hepatocyte-like cells and the methods used to investigate these cells.