Prediction of hepatotoxicity for drugs using human pluripotent stem cell-derived hepatocytes
| Autor: | Jong Hyun Kim, Hee Kyung Park, Min Wang, Jong-Hoon Kim, Kijung Park, Dong Hun Woo, Chungseong Han, Geun Ho An, Jaehun Lee, Xiao Bo Sun, Jeong Seong Kim, Hee Su Hong, Han-Jin Park, Shi Feng Zhu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Drug Pluripotent Stem Cells Cell Survival Health Toxicology and Mutagenesis media_common.quotation_subject Cell Human Embryonic Stem Cells Biology Pharmacology Toxicology Cell Line 03 medical and health sciences 0302 clinical medicine medicine Humans Induced pluripotent stem cell media_common Drug discovery Cell Differentiation Cell Biology Embryonic stem cell In vitro 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Liver 030220 oncology & carcinogenesis Hepatocyte Toxicity Hepatocytes Chemical and Drug Induced Liver Injury |
| Zdroj: | Cell biology and toxicology. 34(1) |
| ISSN: | 1573-6822 |
| Popis: | Drug-induced liver toxicity is a main reason for withdrawals of new drugs in late clinical phases and post-launch of the drugs. Thus, hepatotoxicity screening of drug candidates in pre-clinical stage is important for reducing drug attrition rates during the clinical development process. Here, we show commercially available hepatocytes that could be used for early toxicity evaluation of drug candidates. From our hepatic differentiation technology, we obtained highly pure (≥98%) hepatocytes from human embryonic stem cells (hESCs) having mature phenotypes and similar gene expression profiles with those of primary human tissues. Furthermore, we optimized 96-well culture condition of hESC-derived hepatocytes suitable for toxicity tests in vitro. To this end, we demonstrated the efficacy of our optimized hepatocyte model for predicting hepatotoxicity against the Chinese herbal medicines and showed that toxicity patterns from our hepatocyte model was similar to those of human primary cultured hepatocytes. We conclude that toxicity test using our hepatocyte model could be a good alternative cell source for pre-clinical study to predict potential hepatotoxicity in drug discovery industries. |
| Databáze: | OpenAIRE |
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