Abstract
Human hepatocyte transplantation has been actively perused as an alternative to liver replacement for acute liver failure and liver-based metabolic defects. Current challenges in this field include a limited cell source, reduced cell viability following cryopreservation and poor engraftment of cells into the recipient liver with consequent limited life span. As a result, alternative stem cell sources such as pluripotent stem cells, fibroblasts, hepatic progenitor cells, amniotic epithelial cells and mesenchymal stem/stromal cells (MSCs) can be used to generate induced hepatocyte like cells (HLC) with each technique exhibiting advantages and disadvantages. HLCs may have comparable function to primary human hepatocytes and could offer patient-specific treatment. However, long-term functionality of transplanted HLCs and the potential oncogenic risks of using stem cells have yet to be established. The immunomodulatory effects of MSCs are promising, and multiple clinical trials are investigating their effect in cirrhosis and acute liver failure. Here, we review the current status of hepatocyte transplantation, alternative cell sources to primary human hepatocytes and their potential in liver regeneration. We also describe recent clinical trials using hepatocytes derived from stem cells and their role in improving the phenotype of several liver diseases.
Highlights
The liver is responsible for a diverse range of functions within the body ranging from xenobiotic metabolism to plasma protein synthesis [1]
6 months post-infusion, the child underwent Orthotopic liver transplantation (OLT) and later died. These results suggest that Hepatic progenitor cells (HPC) could play a role in treatment of metabolic liver disease; longerscale clinical trials are required to assess their full potential [65]
Hepatocyte transplantation (HT) offers an alternative therapy to OLT with the aim of treating liver-based metabolic diseases or ALF
Summary
The liver is responsible for a diverse range of functions within the body ranging from xenobiotic metabolism to plasma protein synthesis [1]. 6 months post-infusion, the child underwent OLT and later died These results suggest that HPCs could play a role in treatment of metabolic liver disease; longerscale clinical trials are required to assess their full potential [65]. Zhang et al established in vitro generation of HLCs from human foetal HPCs, under the influence of oncostatin M (OSM), DEX and HGF These newly differentiated hepatocytes have functional glycogen storage, albumin secretion and cytochrome p450 activity with Khuu et al, suggesting that in vitro. Transformed cells generated from this procedure usually exhibit functional hepatic properties 2– 3 weeks post-culturing but do lose functional capabilities when cultured for prolonged periods [69] It is still debated whether MSC-derived hepatocytes are able to efficiently re-populate a host liver to provide adequate function and clinical application is still in its infancy [70]. Digestive Disease Research Center, Shariati Hospital, North Kargar Ave., Tehran, Iran, Islamic Republic
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