Glutathione transferases in hepatocyte-like cells derived from human embryonic stem cells.
Human embryonic stem cells (hESCs) offer a potential unlimited source for functional human hepatocytes, since hESCs can differentiate into hepatocyte-like cells displaying a characteristic hepatic morphology and expressing several hepatic markers. These hepatocyte-like cells could be used in various human in vitro hepatocyte assays, e.g. as a test system for studying drug metabolism and drug-induced hepatotoxicity. Since the toxic effect of a compound is commonly dependent on biotransformation into metabolites, the presence of drug metabolising enzymes in potential test systems must be evaluated. We have investigated the presence of glutathione transferases (GSTs) in hepatocyte-like cells by immunocytochemistry and Western blotting. Results show that these cells have high levels of GSTA1-1, whereas GSTP1-1 is not present in most cases. GSTM1-1 is detected by immunocytochemistry but not by Western blotting. In addition, GST activity is detected in hepatocyte-like cells at levels comparable to human hepatocytes. These results indicate that the hepatocyte-like cells have characteristics that closely resemble those of human adult hepatocytes.
Söderdahl
Therese
T
Department of Biochemical Toxicology, Institute of Environmental Medicine, Nobels Väg 13, Karolinska Institutet, S-17177 Stockholm, Sweden. therese.soderdahl@ki.se
Küppers-Munther
Barbara
B
Heins
Nico
N
Edsbagge
Josefina
J
Björquist
Petter
P
Cotgreave
Ian
I
Jernström
Bengt
B
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D015153:Blotting, Western; D002384:Catalysis; D002478:Cells, Cultured; D015925:Cryopreservation; D053595:Embryonic Stem Cells / Q000201:enzymology*; D051549:Glutathione S-Transferase pi / Q000096:biosynthesis / Q000235:genetics; D005982:Glutathione Transferase / Q000096:biosynthesis* / Q000235:genetics; D006003:Glycogen / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D010503:Periodic Acid-Schiff Reaction
D000199:Actins; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D006003:Glycogen; D007527:Isoenzymes; C496556:GSTP1 protein, human; C119995:glutathione S-transferase alpha