Liver stem cells: a scientific and clinical perspective

The promise of liver stem cells lie in their potential to provide a continual and readily available source of liver cells that can be used for gene therapy, cellular transplant, bioartificial liver-assisted devices, drug toxicology testing and use as an in vitro model to understand the developmental biology of the liver. Both the rodent and human embryonic stem cell, bone marrow hematopoietic stem cell, mesenchymal stem cell, umbilical cord blood cell, fetal liver progenitor cell, adult liver progenitor cell as well as the mature hepatocyte have been reported to be capable of self-renewal, giving rise to daughter hepatocytes both in vivo and in vitro. These cells can repopulate livers in animal models of liver injury and seemingly improve liver function. However, significant challenges still exist before these cells can be used in humans. These include lack of consensus in immunophenotype of liver progenitor cells, uncertainty of the physiological role of reported candidate stem/progenitor cell, practicality in obtaining sufficient quantity of cells for clinical use and concerns over ethics, long-term efficacy and safety. Current molecular techniques of stem cell identification are confounded by cell fusion, horizontal gene transfer, incomplete differentiation and fetal microchimerism. Reports of stem cell transplantation and phase 1 trials of bone marrow transplantation in humans for liver diseases are exciting but require more robust verification. We review the evidence for various candidate stem cells, human clinical trials reported to date and highlight the challenges facing clinicians in their quest to use liver stem cells to save lives.