Donor organ shortage is the main limitation to liver transplantation as a treatment for end‐stage liver disease and acute liver failure. Liver regenerative medicine may in the future offer an alternative form of therapy for these diseases, be it through cell transplantation, bioartificial liver (BAL) devices, or bioengineered whole organ liver transplantation. All three strategies have shown promising results in the past decade. However, before they are incorporated into widespread clinical practice, the ideal cell type for each treatment modality must be found, and an adequate amount of metabolically active, functional cells must be able to be produced. Research is ongoing in hepatocyte expansion techniques, use of xenogeneic cells, and differentiation of stem cell‐derived hepatocyte‐like cells (HLCs). HLCs are a few steps away from clinical application, but may be very useful in individualized drug development and toxicity testing, as well as disease modeling. Finally, safety concerns including tumorigenicity and xenozoonosis must also be addressed before cell transplantation, BAL devices, and bioengineered livers occupy their clinical niche. This review aims to highlight the most recent advances and provide an updated view of the current state of affairs in the field of liver regenerative medicine. Stem Cells 2017;35:42–50

Cell therapy is an emerging form of treatment for several liver diseases, but is limited by the availability of donor livers. Stem cells hold promise as an alternative to the use of primary hepatocytes. We performed an exhaustive review of the literature, with a focus on the latest studies involving the use of stem cells for the treatment of liver disease. Stem cells can be harvested from a number of sources, or can be generated from somatic cells to create induced pluripotent stem cells (iPSCs). Different cell lines have been used experimentally to support liver function and treat inherited metabolic disorders, acute liver failure, cirrhosis, liver cancer, and small-for-size liver transplantations. Cell-based therapeutics may involve gene therapy, cell transplantation, bioartificial liver devices, or bioengineered organs. Research in this field is still very active. Stem cell therapy may, in the future, be used as a bridge to either liver transplantation or endogenous liver regeneration, but efficient differentiation and production protocols must be developed and safety must be demonstrated before it can be applied to clinical practice.

To date, the only curative treatment for end-stage liver disease is liver transplantation, which is limited by the shortage of available organs. Cell therapy, in the form of cell transplantation or cell-based extracorporeal support devices, may in the future offer an alternative to transplantation, or at least provide liver function support as a bridging therapy until surgery may be performed. The purpose of this review is to highlight the most recent advances made in the field of cell therapy and regenerative medicine for the treatment of chronic liver disease. After hepatocyte transplantation, long-term engraftment in the liver and spleen may be achieved, which can be stimulated through preconditioning, multiple infusions, and inflammatory response blockade. Mesenchymal stem cells are promising candidates for cell transplantation, as they have been shown to reduce liver fibrosis and support endogenous regeneration. Adipose tissue-derived stem cells are also being tested in this setting, because of their ready availability. Bioartificial liver devices are being built that allow for effective preservation of hepatocytes, and one such device has recently demonstrated survival benefit in a porcine model of liver failure. Cell transplantation of primary hepatocytes or stem cell-derived hepatocyte-like cells for the treatment of chronic liver disease holds promise. Bioartificial liver systems may in the future be able to bridge acute-on-chronic liver failure patients to liver transplantation.

Inherited metabolic disorders and acute liver failure (ALF) are often indications for liver transplantation in pediatric patients. Liver transplantation, however, is limited by the shortage of donor organs, as well as by the need for chronic immunosuppression. This review focuses on the latest advancements made in the field of liver regenerative medicine as possible future alternatives to pediatric liver transplantation or as a means of temporary liver function support. Cell transplantation offers great promise for the treatment and long-term correction of inherited metabolic disorders, especially when ex vivo gene therapy is combined with autologous hepatocyte or induced pluripotent stem cell (iPSC)-derived hepatocyte-like cell (HLC) transplant. Bioartificial liver (BAL) systems are currently being tested that may be able to bridge patients to either liver transplantation or endogenous liver regeneration, in the case of ALF. Still, further research is required before these forms of cell therapy are incorporated into clinical practice: the optimal cell type for both cell transplantation and BAL systems must be found, methods for the large-scale expansion of these cells must be created, and safety concerns pertaining to each cell type must be addressed.