Cell therapy for liver disease: From liver transplantation to cell factory

• Published in: Journal of hepatology Vol. 62; no. 1; pp. S157 - S169
• Main Authors: Forbes, Stuart J, Gupta, Sanjeev, Dhawan, Anil
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-04-2015
• Subjects: Animals; Cell therapy; Cellular Reprogramming Techniques; Embryonic Stem Cells - transplantation; Gastroenterology and Hepatology; Hepatocytes - transplantation; Humans; Induced Pluripotent Stem Cells - transplantation; Liver cirrhosis; Liver Diseases - therapy; Liver regeneration; Liver Transplantation; Metabolic liver disease; Stem Cell Transplantation; Stem cells; Hepatic progenitor cells; Cell therapy; low-density lipoprotein receptor; Nagase analbuminemic rats; embryonic stem cells; LSEC; liver sinusoidal endothelial cells; iPSCs; MSCs; induced multipotent progenitor cells; ataxia telangiectasia mutant; auxiliary partial orthotopic liver transplantation; OLT; LDLR; iHeps; Good Manufacturing Practice; Orthotopic liver transplantation; VEGF; Watanabe heritable hyperlipidemic cholesterolemic; GMP; FAH; ES Cells; induced hepatocytes; APOLT; fumarylacetoacetate-hydrolase-deficient; mesenchymal stem cells; vascular endothelial growth factor; hepatocyte-like cell; iMPCs; Stem cells; Metabolic liver disease; HPCs; ATM; induced pluripotent stem cells; WHHL; Liver cirrhosis; NAR; HLC; Liver regeneration
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2015.02.040

Summary Work over several decades has laid solid foundations for the advancement of liver cell therapy. To date liver cell therapy in people has taken the form of hepatocyte transplantation for metabolic disorders with a hepatic basis, and for acute or chronic liver failure. Although clinical trials using various types of autologous cells have been implemented to promote liver regeneration or reduce liver fibrosis, clear evidence of therapeutic benefits have so far been lacking. Cell types that have shown efficacy in preclinical models include hepatocytes, liver sinusoidal endothelial cells, mesenchymal stem cells, endothelial progenitor cells, and macrophages. However, positive results in animal models have not always translated through to successful clinical therapies and more realistic preclinical models need to be developed. Studies defining the optimal repopulation by transplanted cells, including routes of cell transplantation, superior engraftment and proliferation of transplanted cells, as well as optimal immunosuppression regimens are required. Tissue engineering approaches to transplant cells in extrahepatic locations have also been proposed. The derivation of hepatocytes from pluripotent or reprogramed cells raises hope that donor organ and cell shortages could be overcome in the future. Critical hurdles to be overcome include the production of hepatocytes from pluripotent cells with equal functional capacity to primary hepatocytes and long-term phenotypic stability in vivo.