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On-line Access: 2021-02-08
Received: 2020-10-20
Revision Accepted: 2020-12-15
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3D human nonalcoholic hepatic steatosis and fibrosis models
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Sushila Maharjan, Diana Bonilla, Princy Sindurakar, Hongbin Li, Wanlu Li, Sergio Duarte, Ali Zarrinpar & Y. Shrike Zhang . 3D human nonalcoholic hepatic steatosis and fibrosis models[J]. Journal of Zhejiang University Science D, 2021, 4(2): 157-170.
@article{title="3D human nonalcoholic hepatic steatosis and fibrosis models",
author="Sushila Maharjan, Diana Bonilla, Princy Sindurakar, Hongbin Li, Wanlu Li, Sergio Duarte, Ali Zarrinpar & Y. Shrike Zhang ",
journal="Journal of Zhejiang University Science D",
volume="4",
number="2",
pages="157-170",
year="2021",
publisher="Zhejiang University Press & Springer",
doi="10.1007/s42242-020-00121-4"
}
%0 Journal Article
%T 3D human nonalcoholic hepatic steatosis and fibrosis models
%A Sushila Maharjan
%A Diana Bonilla
%A Princy Sindurakar
%A Hongbin Li
%A Wanlu Li
%A Sergio Duarte
%A Ali Zarrinpar & Y. Shrike Zhang
%J Journal of Zhejiang University SCIENCE D
%V 4
%N 2
%P 157-170
%@ 1869-1951
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1007/s42242-020-00121-4
TY - JOUR
T1 - 3D human nonalcoholic hepatic steatosis and fibrosis models
A1 - Sushila Maharjan
A1 - Diana Bonilla
A1 - Princy Sindurakar
A1 - Hongbin Li
A1 - Wanlu Li
A1 - Sergio Duarte
A1 - Ali Zarrinpar & Y. Shrike Zhang
J0 - Journal of Zhejiang University Science D
VL - 4
IS - 2
SP - 157
EP - 170
%@ 1869-1951
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1007/s42242-020-00121-4
Abstract: This study presents a simple and robust three-dimensional human hepatic tissue model to emulate steatotic and fibrotic conditions and provide an in vitro model for drug testing and mechanistic studies. Using a photolithographic biofabrication method with a photomask featuring hexagonal units, liver cells, including a human hepatic cell line (HepG2-C3A) and a human hepatic stellate cell line (LX-2) were embedded in gelatin methacryloyl hydrogel. Hepatic steatosis was induced by supraphysiological concentration of free fatty acids; hepatic fibrosis was induced by transforming growth factor-?1. Induction of steatosis was confirmed by Oil Red O and BODIPY staining and was inhibited with toyocamycin and obeticholic acid. Induction of fibrosis was confirmed by immunostaining for collagen type I and alpha smooth muscle actin and inhibited by rapamycin and curcumin treatment. This model was further preliminarily validated using primary human hepatocytes in a similar setup. These constructs provide a viable, biologically relevant, and higher throughput model of hepatic steatosis and fibrosis and may facilitate the study of the mechanisms of disease and testing of liver-directed drugs.
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