Differentiation of Monkey Embryonic Stem Cells to Hepatocytes by Feeder-free Dispersion Culture and Expression Analyses of Cytochrome P450 Enzymes Responsible for Drug Metabolism
スポンサーリンク
概要
- 論文の詳細を見る
We reported previously that monkey embryonic stem cells (ESCs) were differentiated into hepatocytes by formation of embryoid bodies (EBs). However, this EB formation method is not always efficient for assays using a large number of samples simultaneously. A dispersion culture system, one of the differentiation methods without EB formation, is able to more efficiently provide a large number of feeder-free undifferentiated cells. A previous study demonstrated the effectiveness of the Rho-associated kinase inhibitor Y-27632 for feeder-free dispersion culture and induction of differentiation of monkey ESCs into neural cells. In the present study, the induction of differentiation of cynomolgus monkey ESCs (cmESCs) into hepatocytes was performed by the dispersion culture method, and the expression and drug inducibility of cytochrome P450 (CYP) enzymes in these hepatocytes were examined. The cmESCs were successfully differentiated into hepatocytes under feeder-free dispersion culture conditions supplemented with Y-27632. The hepatocytes differentiated from cmESCs expressed the mRNAs for three hepatocyte marker genes (a-fetoprotein, albumin, CYP7A1) and several CYP enzymes, as measured by real-time polymerase chain reaction. In particular, the basal expression of cmCYP3A4 (3A8) in these hepatocytes was detected at mRNA and enzyme activity (testosterone 6β-hydroxylation) levels. Furthermore, the expression and activity of cmCYP3A4 (3A8) were significantly upregulated by rifampicin. These results indicated the effectiveness of Y-27632 supplementation for feeder-free dispersed culture and induction of differentiation into hepatocytes, and the expression of functional CYP enzyme(s) in cmESC-derived hepatic cells.
著者
-
Yamaori Satoshi
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Hokuriku University
-
Maruyama Junya
Department Of Medicinal Chemistry And Clinical Pharmacy School Of Pharmacy Tokyo University Of Pharm
-
OHMORI Shigeru
Department of Biochemical Pharmacology and Biotoxicology, Faculty of Pharmaceutical Sciences, Chiba University
-
Nakamura Katsunori
Graduate School of Pharmaceutical Sciences, Nagoya City University
-
Matsunaga Tamihide
Graduate School of Pharmaceutical Sciences, Nagoya City University
-
Maruyama Junya
Department of Pharmacy, Shinshu University Hospital
-
Sakamoto Sakae
Kissei Pharmaceutical Co., Ltd.
-
Kamada Noboru
Kissei Pharmaceutical Co., Ltd.
-
Kikuchi Shinji
Kissei Pharmaceutical Co., Ltd.
関連論文
- Role of Dexamethasone and Oncostatin M on the Formation of Vacuoles in Human Fetal Liver Cells(Molecular and Cell Biology)
- Butyrylcholinesterase and Erythrocyte Sulfhydryl-dependent Enzyme Hydrolyze Gabexate in Human Blood
- Involvement of Human Blood Arylesterases and Liver Microsomal Carboxylesterases in Nafamostat Hydrolysis
- Hepatic Metabolism of Methyl Anthranilate and Methyl N-Methylanthranilate as Food Flavoring Agents in Relation to Allergenicity in the Guinea Pig
- Stereospecific and Regioselective Hydrolysis of Cannabinoid Esters by ES46.5K, an Esterase from Mouse Hepatic Microsomes, and Its Differences from Carboxylesterases of Rabbit and Porcine Liver(Biochemistry)
- In Vitro Inhibitory Effects of Cannabinoids on Progesterone 17α-Hydroxylase Activity in Rat Testis Microsomes
- Comparison of Basal Gene Expression and Induction of CYP3As in HepG2 and Human Fetal Liver Cells(Pharmacology)
- The Effects of Japanese Herbal Medicines on Drug Oxidations in Rat Liver Microsomes in vitro
- Effects of Kampo Extracts on Drug Metabolism in Rat Liver Microsomes: Rhei Rhizoma Extract and Glycyrrhizae Radix Extract Inhibit Drug Oxidation
- Effect of Grapefruit Juice on the Urinary 6β-hydroxycortisol/cortisol Ratio
- Formation of large vacuoles induced by cooperative effects of oncostatin M and dexamethasone in human fetal liver cells
- Cytochrome P450 3As Gene Expression and Testosterone 6β-Hydroxylase Activity in Human Fetal Membranes and Placenta at Full Term
- Expression of Cytochrome P450 and Transcription Factors during In Vitro Differentiation of Mouse Embryonic Stem Cells into Hepatocytes
- Differentiation of Monkey Embryonic Stem Cells into Hepatocytes and mRNA Expression of Cytochrome P450 Enzymes Responsible for Drug Metabolism : Comparison of Embryoid Body Formation Conditions and Matrices(Pharmacology)
- Altered Pharmacokinetics of Prednisolone and Cortisol Suppression During Oral Prednisolone Therapy in Patients with Nephrotic Syndrome
- Influence of Cytochrome P450 2C19 Gene Variations on Pharmacokinetic Parameters of Thalidomide in Japanese Patients
- Differentiation of Monkey Embryonic Stem Cells to Hepatocytes by Feeder-free Dispersion Culture and Expression Analyses of Cytochrome P450 Enzymes Responsible for Drug Metabolism
- Structural Requirements for Potent Direct Inhibition of Human Cytochrome P450 1A1 by Cannabidiol: Role of Pentylresorcinol Moiety
- Plasma glutathione S-transferase in carbon tetrachrolide treated rats and its association to hepatic cytosolic isozymes.