Prediction of hepatotoxicity for drugs using human pluripotent stem cell-derived hepatocytes |
| |
Authors: | Jong Hyun Kim Min Wang Jaehun Lee Han-Jin Park Chungseong Han Hee Su Hong Jeong Seong Kim Geun Ho An Kijung Park Hee-Kyung Park Shi Feng Zhu Xiao-Bo Sun Jong-Hoon Kim Dong-Hun Woo |
| |
Affiliation: | 1.Laboratory of Stem Cells,NEXEL Co., Ltd.,Seoul,South Korea;2.Institute of Medicinal Plant Development (IMPLAD),Chinese Academy of Medical Sciences/Peking Union Medical College (CAMS/PUMC),Beijing,China;3.Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus,Korea University,Seoul,South Korea;4.Predictive Model Research Center,Korea Institute of Toxicology,Daejeon,South Korea;5.Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute,Seoul National University,Seoul,South Korea;6.School of Continuing Education,Yanbian University,Yanji City,China |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|