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.
Keywords: Acute liver failure, Bioartificial liver, Cell therapy, Hepatic
differentiation, Hepatocyte-like cells, Hepatocytes, Immunogenicity, Induced pluripotent stem cells, Liver diseases, Microencapsulation, Pluripotent stem cells,
Tumorigenicity.
