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Embryonic Stem Cells/Induced Pluripotent Stem Cells
Article first published online: 4 FEB 2010
Copyright © 2010 AlphaMed Press
Volume 28, Issue 4, pages 674–686, April 2010
How to Cite
Duan, Y., Ma, X., Zou, W., Wang, C., Bahbahan, I. S., Ahuja, T. P., Tolstikov, V. and Zern, M. A. (2010), Differentiation and Characterization of Metabolically Functioning Hepatocytes from Human Embryonic Stem Cells. STEM CELLS, 28: 674–686. doi: 10.1002/stem.315
Author contributions: Y.D.: Conception and design, execution and collection of data, data analysis and interpretation, manuscript writing, partial financial support; X.M.: Experimental design, provision of study materials, execution and collection of data; Y.D. and X.M. contributed equally to this work; W.Z.: Execution of data, data analysis, assisting in manuscript writing; C.W., I.S.B., and T.A.: Execution of data; V.T.: Facility and partial financial support; M.Z.: Conception and design, laboratory facility and full financial support, final approval of manuscript.
First published online in STEM CELLS EXPRESS February 4, 2010.
Disclosure of potential conflicts of interest is found at the end of this article.
- Issue published online: 14 APR 2010
- Article first published online: 4 FEB 2010
- Manuscript Accepted: 19 JAN 2010
- Manuscript Received: 15 SEP 2009
- NIH. Grant Number: DK075415
- California Institute of Regenerative Medicine. Grant Number: RC1-00359
- Alpha-1 Foundation
- UC Davis Genome Center
Vol. 29, Issue 9, 1476, Article first published online: 19 AUG 2011
- Human embryonic stem cells;
- Hepatic differentiation;
- Metabolic profiling;
- Metabolic function;
Human embryonic stem cells (hESCs) may provide a cell source for functional hepatocytes for clinical applications and drug development. Initially, the hESC population was enriched to be more than 85% definitive endoderm (DE) as assessed by the expression of CXCR4, SOX17, and FOXA2. We then successfully converted DE into hepatic progenitors with 93% of the cells being positive for α-feto protein within 9 days. The percentage of albumin positive cells gradually increased to 90% at days 20-22 after differentiation. Moreover, our hESC-derived hepatocytes (hEH) developed a complete biotransformation system including phase I and II metabolizing enyzmes and phase III transporters. Nuclear receptors, which are critical in regulating the expression of metabolizing enzymes, were also expressed by our hEH. Using ultraperformance liquid chromatography-tandem mass spectrometry technology, we identified seven metabolic pathways of the drug bufuralol including four newly-reported ones in our hEH, which are the same as those in freshly isolated human primary hepatocytes (hPH). In addition, the results of the metabolism of four drugs indicate that our hEH have the capacity to metabolize these drugs at levels that are comparable to hPH. In conclusion, we have generated a relatively homogenous population of hepatocytes from hESCs, which appear to have complete metabolic function that is comparable to primary liver cells. These results represent a significant step towards the efficient differentiation of mature hepatocytes for cell-based therapeutics as well as for pharmacology and toxicology studies. STEM CELLS 2010;28:674–686