title: Prediction of hepatotoxicity for drugs using human pluripotent stem cell-derived hepatocytes.
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.
authors.affiliation: Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea.
authors.forename: Jong Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences/Peking Union Medical College (CAMS/PUMC), No 151, North Road Malianwa, Haidian District, Beijing, 100093, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, South Korea.
authors.forename: Jaehun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Predictive Model Research Center, Korea Institute of Toxicology, Daejeon, 34114, South Korea.
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea.
authors.forename: Chungseong
authors.initials: C
authors.lastname: Han
authors.affiliation: Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea.
authors.forename: Hee Su
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea.
authors.forename: Jeong Seong
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea.
authors.forename: Geun Ho
authors.initials: GH
authors.lastname: An
authors.affiliation: Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea.
authors.forename: Kijung
authors.initials: K
authors.lastname: Park
authors.affiliation: Department of Oral Medicine and Oral Diagnosis, School of Dentistry and Dental Research Institute, Seoul National University, Yunkeun-dong 28, Chongro-Ku, Seoul, 03080, South Korea.
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Park
authors.affiliation: School of Continuing Education, Yanbian University, 977 Gongyuan Str, Yanji City, Jilin Province, 133002, China.
authors.forename: Shi Feng
authors.initials: SF
authors.lastname: Zhu
authors.affiliation: Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences/Peking Union Medical College (CAMS/PUMC), No 151, North Road Malianwa, Haidian District, Beijing, 100093, China. sun-xiaobo@163.com.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Sun
authors.affiliation: Laboratory of Stem Cells and Tissue Regeneration, Department of Biotechnology, College of Life Sciences and Biotechnology, Science Campus, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, South Korea. jhkim@korea.ac.kr.
authors.forename: Jong-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Laboratory of Stem Cells, NEXEL Co., Ltd., 9th floor, 21 Wangsan-ro, Dongdaemun-gu, Seoul, 02580, South Korea. dhwoo@nexel.co.kr.
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Woo
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000473:pathology*; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000473:pathology*; D000066449:Human Embryonic Stem Cells / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology*; D039904:Pluripotent Stem Cells / Q000473:pathology*
keywords: Drug screening; Hepatocytes; Human embryonic stem cells; Toxicity test