Improving albumin production of hepatic lineage cells from mouse embryonic stem cells in vitro

Embryonic stem (ES) cells can differentiate into hepatic lineage cells in vitro and can potentially be used as source of hepatocytes in research and therapy. A good source of ES cell-derived hepatocytes with greater liver function may be needed when attempting to transplant hepatocytes or use bioartificial livers to treat liver disease. This in vitro study explores the use of mouse ES cells to derive hepatic lineage cells able to produce greater levels albumin. To do this we designed a series of experimental studies and developed a refined culture method which involved adjusting the composition of culture medium and the time that it would be used. The embryoid bodies (EBs) cultured by this method produced hepatic lineage cells capable of producing high amounts of albumin (1.90 ± 0.198 pg/h cell). These cells, which were able to uptake indocyanine green (ICG), expressed the hepatic genes α1-anti-trypsin (AAT), α-fetoprotein (AFP), albumin, carbamoyl-phosphate synthetase 1 (CPS1), cytochrome P450 7A1 (CYP7A1), glucose-6-phosphatase (G6P), tyrosine aminotransferase (TAT), tryptophan 2,3-dioxygenase (TDO2), and transthyretin (TTR). In conclusion, we found that this method allowed us to effectively derive high albumin-producing ES cell-derived hepatic lineage cells for experimental and clinical use.