Stem cell therapy for chronic liver disease—choosing the right tools for the job
- Professor Stuart J Forbes, MRC/University of Edinburgh Centre for Inflammation Research, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK;
The liver has a fantastic regenerative capacity but, following chronic liver damage, this begins to fail, and then fibrosis, and eventually cirrhosis, develops.1 Currently the only curative treatment for advanced liver cirrhosis is liver transplant. Although liver transplant has become a procedure with a relatively good 5-year survival, organ donation has not kept up with demand, which has resulted in an increasing number of patients on the liver transplant waiting list waiting longer for a donor organ, which leads to increased morbidity and mortality.2 Furthermore it is estimated that over the next few years there will be a 5-fold increase in the need for liver transplantation in the UK.3 Although there is emerging evidence that extending the donor organ criteria may impact on this mortality rate,4 there is clearly still an urgent need to develop alternative strategies for the treatment of advanced liver disease, and numerically cirrhosis is the most important target. It is with this background that there has been understandable enthusiasm for the development of stem cell therapies for liver regeneration.
Bone marrow (BM) stem cells have been intensively investigated as a potential source of liver stem cells and as a means to regenerate the cirrhotic liver, and it is worth briefly outlining why they have attracted this attention. There are a population of intrahepatic progenitor cells, termed oval cells in rodents, which can take over liver regeneration when the usual mode of regeneration, via division of mature hepatocytes, begins to fail. It was suggested some time ago that these cells expressed the haematopoeitic stem cell marker THY-15 (though this is now disputed), and it was therefore postulated that these oval cells were originating from the BM. Indeed initial experiments supported this hypothesis.6 Furthermore, following analysis of both mouse BM transplant models …