Highly Efficient Differentiation of Functional Hepatocytes From Human Induced Pluripotent Stem Cells

摘要: Human induced pluripotent stem cells (hiPSCs) hold great potential for use in regenerative medicine, novel drug development, and disease progression/developmental studies. Here, we report highly efficient differentiation of hiPSCs toward a relatively homogeneous population functional hepatocytes. hiPSC-derived hepatocytes (hiHs) not only showed high expression hepatocyte-specific proteins liver-specific functions, but they also developed biotransformation system including phase I II metabolizing enzymes III transporters. Nuclear receptors, which are critical regulating the enzymes, were expressed hiHs. hiHs responded to different compounds/inducers cytochrome P450 as mature do. To follow up on this observation, analyzed capacity real time using ultraperformance liquid chromatography-tandem mass spectrometry. We found that, like freshly isolated primary human hepatocytes, seven major metabolic pathways bufuralol In addition, transplanted engrafted, integrated, proliferated livers an immune-deficient mouse model, secreted albumin, indicating that function vivo. conclusion, have generated method generation from vitro vivo, it appears similarly developing complete function. These results represent significant step patient/disease-specific cell-based therapeutics well pharmacology toxicology