الفهرس | Only 14 pages are availabe for public view |
Abstract Due to the increasing demand of liver transplantation as the only proven cure for end stage liver diseases and the limited supply of viable livers, many researchers believe that the solution lies in transplanting a line of immortalized hepatocyte-like cells derived from human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Unfortunately, the presently available approaches to differentiate the cells towards a hepatocyte lineage are not adequate and are not GMP-compatible; thus they are still far from being accepted by the FDA for advancing to clinical trials. I try here to identify the major histone demethylases that participate in the differentiation of stem cells to definitive endoderm (DE) as a first step in collecting the data that will enable us one day to manipulate the epigenetic factors during the differentiation process to produce more functional hepatocyte cells. In addition, I describe our approach to establish a xeno-free feeder-free culture protocol that will be GMP-compatible that may be acceptable for use in clinical trials in humans. Finally, I describe our use of a bioreactor to scale up the production of the stem cells in order to obtain enough hepatocytes which can be used for liver cell transplantation and bio-artificial liver support devices, as well as for toxicology and pharmacology studies. |