Abstract
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.
Highlights
As of today, liver transplantation is the only proven treatment for a wide variety of liver diseases refractory to medical treatment
Isolated primary hepatocytes were the first type of cell to be tested in both in vivo and ex vivo cell therapies, but their use has been limited by a number of technical difficulties that have yet to be overcome
We address the advantages and limitations of each cell line, as well as the different liver diseases that may be able to benefit from stem cell therapy
Summary
Liver transplantation is the only proven treatment for a wide variety of liver diseases refractory to medical treatment. The demand for donor organs considerably exceeds their supply, making therapeutic alternatives to whole-organ liver transplantation necessary. Isolated primary hepatocytes were the first type of cell to be tested in both in vivo and ex vivo cell therapies, but their use has been limited by a number of technical difficulties that have yet to be overcome. The main limitation for their use, is that clinical demand for hepatocytes cannot be met due to a scarcity of donor livers from which high-quality primary hepatocytes can be isolated. The capacity of stem cells for differentiation and self-renewal make them a plausible source for the generation of unlimited numbers of hepatocytes. We address the advantages and limitations of each cell line, as well as the different liver diseases that may be able to benefit from stem cell therapy
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