title: Enhancement of hepatocyte differentiation from human embryonic stem cells by Chinese medicine Fuzhenghuayu.
abstract: Chinese medicine, Fuzhenghuayu (FZHY), appears to prevent fibrosis progression and improve liver function in humans. Here we found that FZHY enhanced hepatocyte differentiation from human embryonic stem cells (hESC). After treatment with FZHY, albumin expression was consistently increased during differentiation and maturation process, and expression of metabolizing enzymes and transporter were also increased. Importantly, expression of mesenchymal cell and cholangiocyte marker was significantly reduced by treatment with FZHY, indicating that one possible mechanism of FZHY's role is to inhibit the formation of mesenchymal cells and cholangiocytes. Edu-labelled flow cytometric analysis showed that the percentage of the Edu positive cells was increased in the treated cells. These results indicate that the enhanced proliferation involved hepatocytes rather than another cell type. Our investigations further revealed that these enhancements by FZHY are mediated through activation of canonical Wnt and ERK pathways and inhibition of Notch pathway. Thus, FZHY not only promoted hepatocyte differentiation and maturation, but also enhanced hepatocyte proliferation. These results demonstrate that FZHY appears to represent an excellent therapeutic agent for the treatment of liver fibrosis, and that FZHY treatment can enhance our efforts to generate mature hepatocytes with proliferative capacity for cell-based therapeutics and for pharmacological and toxicological studies.
authors.affiliation: Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China.|Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA.|Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, USA.|Department of Dermatology, University of California Davis Medical Center, Sacramento, California, USA.
authors.forename: Jiamei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA.|Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, USA.|Institute of Biophysics, the Chinese Academy of Science, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA.|Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA.|Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, USA.
authors.forename: Xiaocui
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA.|Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tschudy-Seney
authors.affiliation: Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China.|E-institutes of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Chenghai
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA.|Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Zern
authors.affiliation: Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai, China.|E-institutes of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine, University of California Davis Medical Center, Sacramento, California, USA.|Institute for Regenerative Cures, University of California Davis Medical Center, Sacramento, California, USA.|Department of Dermatology, University of California Davis Medical Center, Sacramento, California, USA.
authors.forename: Yuyou
authors.initials: Y
authors.lastname: Duan
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000066449:Human Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects
chemical_list: D004365:Drugs, Chinese Herbal