Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Generation of uniform liver spheroids from human pluripotent stem cells for imaging-based drug toxicity analysis

Authors
Lee, GyunggyuKim, HyeminPark, Ji YoungKim, GyeongminHan, JiyouChung, SeokYang, Ji HunJeon, Jang SuWoo, Dong-HunHan, ChoongseongKim, Sang KyumPark, Han-JinKim, Jong-Hoon
Issue Date
2월-2021
Publisher
ELSEVIER SCI LTD
Keywords
Stem cell; Spheroid; Microwell; Hepatocyte; Toxicity
Citation
BIOMATERIALS, v.269
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
269
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/50017
DOI
10.1016/j.biomaterials.2020.120529
ISSN
0142-9612
Abstract
Recent advances in pluripotent stem cell technology provide an alternative source of human hepatocytes to overcome the limitations of current toxicity tests. However, this approach requires optimization and standardization before it can be used as a fast and reliable toxicity screening system. Here, we designed and tested microwell culture platforms with various diameters. We found that large quantities of uniformly-sized hepatocyte-like cell (HLC) spheroids (3D-uniHLC-Ss) could be efficiently and reproducibly generated in a short period time from a small number of differentiating human pluripotent stem cells (hPSCs). The hPSC-3D-uniHLC-Ss that were produced in 500-mu m diameter microwells consistently exhibited high expressions of hepatic marker genes and had no significant signs of cell death. Importantly, a hepatic master gene hepatocyte nuclear factor 4 alpha (HNF4 alpha) was maintained at high levels, and the epithelial-mesenchymal transition was significantly attenuated in hPSC-3D-uniHLC-Ss. Additionally, when compared with 3D-HLC-Ss that were produced in other 3D platforms, hPSC-3D-uniHLC-Ss showed significantly higher hepatic gene expressions and drug-metabolizing activity of the enzyme, CYP3A4. Imaging-based drug toxicity studies demonstrated that hPSC-3D-uniHLC-Ss exhibited enhanced sensitivity to various hepatotoxicants, compared to HLCs, which were differentiated under 2D conditions. Precise prediction of drug-induced hepatotoxicity is a crucial step in the early phases of drug discovery. Thus, the hPSC-3D-uniHLC-Ss produced using our microwell platform could be used as an imaging-based toxicity screening system to predict drug hepatotoxicity.
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Engineering > Department of Mechanical Engineering > 1. Journal Articles
Graduate School > Department of Biotechnology > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Chung, Seok photo

Chung, Seok
공과대학 (기계공학부)
Read more

Altmetrics

Total Views & Downloads

BROWSE