Abstract:
OBJECTIVES:The aim of the study is to generate a spherical three-dimensional (3D) aggregate of hepatocyte-like cells (HLCs) differentiated from human embryonic stem cells and to investigate the effect of the 3D environment on hepatic maturation and drug metabolism. RESULTS:Quantitative real-time PCR analysis indicated that gene expression of mature hepatocyte markers, drug-metabolizing enzymes, and hepatic transporters was significantly higher in HLCs cultured in the 3D system than in those cultured in a two-dimensional system (p < 0.001). Moreover, hepatocyte-specific functions, including albumin secretion and bile canaliculi formation, were increased in HLCs cultured in the 3D system. In particular, 3D spheroidal culture increased expression of CES1 and BCHE, which encode hepatic esterases (p < 0.001). The enhanced activities of these hepatic esterases were confirmed by the cholinesterase activity assay and the increased susceptibility of HLCs to oseltamivir, which is metabolized by CES1. CONCLUSIONS:3D spheroidal culture enhances the maturation and drug metabolism of stem cell-derived HLCs, and this may help to optimize hepatic differentiation protocols for hepatotoxicity testing.
journal_name
Biotechnol Lettjournal_title
Biotechnology lettersauthors
Choi YJ,Kim H,Kim JW,Yoon S,Park HJdoi
10.1007/s10529-018-2528-1subject
Has Abstractpub_date
2018-05-01 00:00:00pages
755-763issue
5eissn
0141-5492issn
1573-6776pii
10.1007/s10529-018-2528-1journal_volume
40pub_type
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