Cell therapy for liver disease: From liver transplantation to cell factory.
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 reprogrammed 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.
MRC Centre for Regenerative Medicine, Scottish Centre for Regenerative Medicine, 5 Little France Drive, Edinburgh EH16 4UU, United Kingdom. Electronic address: stuart.forbes@ed.ac.uk.
Stuart J
SJ
Forbes
Departments of Medicine and Pathology, Albert Einstein College of Medicine, Jack and Pearl Resnick Campus, 1300 Morris Park Avenue, Ullmann Building, Room 625, Bronx, NY 10461, United States.
Sanjeev
S
Gupta
Paediatric Liver GI and Nutrition Center and NIHR/Wellcome Cell Therapy Unit, King's College Hospital at King's College, London SE59RS, United Kingdom.
Anil
A
Dhawan
D000818:Animals; D000067470:Cellular Reprogramming Techniques; D053595:Embryonic Stem Cells / Q000637:transplantation; D022781:Hepatocytes / Q000637:transplantation*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000637:transplantation; D008107:Liver Diseases / Q000628:therapy*; D016031:Liver Transplantation; D033581:Stem Cell Transplantation
Cell therapy; Liver cirrhosis; Liver regeneration; Metabolic liver disease; Stem cells