The generation of hepatocytes from mesenchymal stem cells and engraftment into the liver

Liver transplantation is the ultimate therapeutic option for the treatment of end-stage liver diseases, which, however, is restricted by the shortage of donor organs. Instead hepatocyte transplantation seemed to be a way out, but again marginal donor livers for the isolation of primary human hepatocytes are scarce. The hepatocyte differentiation capacity of mesenchymal stem cells might open a new cell resource to generate hepatocyte-like cells for therapeutical use.

Apart from their potency of hepatocyte differentiation mesenchymal stem cells display pleiotropic biological features including modulation of immunogenicity, anti-inflammatory and anti-apoptotic as well as pro-proliferative impact at the site of tissue or organ lesions. They are mobilized from the bone marrow and migrate to the liver along chemoattractive gradients thus contributing to the humoral and cellular response in tissue repair. The cause of different liver diseases is varying depending on, for example, viral, toxic, nutritional, neoplastic challenges. As known from animal studies mesenchymal stem cells seem to have a beneficial impact on liver regeneration and tissue repair under a variety of liver disease conditions.

Their versatile biological features render mesenchymal stem cells an alternate cell resource for the treatment of liver diseases. It is important to know the mechanisms of integration of transplanted cells into the recipient tissue and to understand the communication between donor cells and the host tissue on the molecular level in order to support efficacy of cell transplantation and thus optimize the therapeutical outcome.