Induced pluripotent stem cells for the treatment of liver diseases: challenges and perspectives from a clinical viewpoint

The only curative treatment for severe end-stage liver disease (ESLD) is liver transplantation (LT) but it is limited by the shortage of organ donors. The increase of the incidence of liver disease has led to develop new therapeutic approaches such as liver cell transplantation. Current challenges that limit a wider application of this therapy include a limited cell source and the poor engraftment in the host liver of cryopreserved hepatocytes after thawing. Induced pluripotent stem cells (iPSCs) that can be differentiated into hepatocyte-like cells (HLCs) are being widely explored as an alternative to human hepatocytes because of their unlimited proliferation capacity and their potential ability to avoid the immune system. Their large-scale production could provide a new tool to produce enough HLCs for treating patients with metabolic diseases, acute liver failure (ALF), those with ESLD or patients not considered for organ transplantation. In this review we discuss current challenges for generating differentiated cells compatible with human application as well as in-depth safety evaluation. This analysis highlights the uncertainties and deficiencies that should be addressed before their clinical use but also points out the potential benefits that will produce a great impact in the field of hepatology.