Abstract

Cell-based liver therapies are envisaged as a useful therapeutic option to supplement or replace whole organ transplantation by recovering and stabilizing the lost metabolic function for acute and chronic liver diseases. However, success is hampered by the scarce availability of liver tissue to isolate good-quality cells, and by insufficient cell engraftment mainly due to rejection of transplanted cells. Thus new cell sources alternatives to hepatocytes are being considered to obtain more sustained and significant hepatic metabolic correction, and to reduce the waiting-list mortality rate. Human pluripotent stem cells with hepatic differentiation potential represent a valuable cell source for generating large numbers of functional hepatocyte-like cells for liver cell therapy. The immunogenicity and tumorigenicity of these cells are still a bottleneck for successful clinical application. The preclinical proof-of-concept that pluripotent stem cell-derived hepatocytes can improve disease in animal models is being investigated to fully establish efficacy and safety before conducting welldesigned clinical trials. More recent developments in bioengineering and regenerative medicine to augment or replace liver function have extended several complex cellbased approaches to treat liver disease [bioartificial liver devices and bioengineered organs]. Such new strategies offer an alternative to organ transplantation in patients with liver diseases and are currently being rigorously tested and validated in preclinical studies before being safely transferred to the clinical practice.