In vivo reprogramming of hepatic myofibroblasts into hepatocytes attenuates liver fibrosis: back to the future?
Orthotopic liver transplantation (OLT) represents the standard curative treatment for human patients affected by an end-stage form of life-threatening liver disease involving, whatever the etiology (acquired or inborn) and development (acute or chronic), significant loss of hepatocytes and organ failure (1,2). The need for reliable therapeutic approaches alternative to OLT, in particular involving cell therapy, has become progressively more urgent because of the increasing worldwide incidence of liver diseases, particularly end-stage chronic liver diseases (CLDs), which is unfortunately associated to a significant shortage in organ availability (1,2). In the last two decades, several laboratories have performed studies designed to establish cell therapy procedures able to provide stable and reliable sources of functional hepatocytes or of hepatocyte-like cells (HLCs) to be used for repopulation of damaged liver parenchyma. To this purpose intra- or extrahepatic cells have been used in pre-clinical studies as a potential source of functional HLCs to be transplanted, including primary hepatocytes, liver sinusoidal-endothelial cells, mesenchymal stem cells, endothelial progenitor cells, liver progenitor cells and even macrophages. However, due to several limitations [reviewed in (3-6)], these procedures offered sometimes positive results in animal models but, with few limited exceptions, were not always translated to successful clinical therapeutic approaches.