Prediction of interindividual differences in hepatic functions and drug sensitivity by using human iPS-derived hepatocytes

K Takayama, Y Morisaki, S Kuno… - Proceedings of the …, 2014 - National Acad Sciences
K Takayama, Y Morisaki, S Kuno, Y Nagamoto, K Harada, N Furukawa, M Ohtaka…
Proceedings of the National Academy of Sciences, 2014National Acad Sciences
Interindividual differences in hepatic metabolism, which are mainly due to genetic
polymorphism in its gene, have a large influence on individual drug efficacy and adverse
reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem
(iPS) cells have the potential to predict interindividual differences in drug metabolism
capacity and drug response. However, it remains uncertain whether human iPSC-derived
HLCs can reproduce the interindividual difference in hepatic metabolism and drug …
Interindividual differences in hepatic metabolism, which are mainly due to genetic polymorphism in its gene, have a large influence on individual drug efficacy and adverse reaction. Hepatocyte-like cells (HLCs) differentiated from human induced pluripotent stem (iPS) cells have the potential to predict interindividual differences in drug metabolism capacity and drug response. However, it remains uncertain whether human iPSC-derived HLCs can reproduce the interindividual difference in hepatic metabolism and drug response. We found that cytochrome P450 (CYP) metabolism capacity and drug responsiveness of the primary human hepatocytes (PHH)-iPS-HLCs were highly correlated with those of PHHs, suggesting that the PHH-iPS-HLCs retained donor-specific CYP metabolism capacity and drug responsiveness. We also demonstrated that the interindividual differences, which are due to the diversity of individual SNPs in the CYP gene, could also be reproduced in PHH-iPS-HLCs. We succeeded in establishing, to our knowledge, the first PHH-iPS-HLC panel that reflects the interindividual differences of hepatic drug-metabolizing capacity and drug responsiveness.
National Acad Sciences