3D human nonalcoholic hepatic steatosis and fibrosis models  

作　　者：Sushila Maharjan Diana Bonilla Princy Sindurakar Hongbin Li Wanlu Li Sergio Duarte Ali Zarrinpar Y.Shrike Zhang 

机构地区：[1]Division of Engineering in Medicine,Department of Medicine,Brigham and Women’s Hospital,Harvard Medical School,65 Landsdowne St,Cambridge,MA 02139,USA [2]Department of Biology,College of the Holy Cross,Worcester,MA 01610,USA [3]Department of Surgery,University of Florida,1600 SW Archer Rd,Gainesville,FL 32610,USA [4]Department of Biomedical Engineering,University of Florida,Gainesville,FL 32610,USA [5]Department of Biochemistry and Molecular Biology,University of Florida,Gainesville,FL 32610,USA

出　　处：《Bio-Design and Manufacturing》2021年第2期157-170,共14页生物设计与制造（英文）

基　　金：YSZ received funding from National Institutes of Health(K99CA201603,R00CA201603,R21EB025270,R21EB026175,R01EB028143,R03EB027984);National Science Foundation(1935105);Brigham Research Institute New England Anti-Vivisection Foundation,and American Fund for Alternatives to Animal Research(AFAAR).AZ received funding from National Institutes of Health(K08DK113244,R01MD012579);SD received funding from National Institutes of Health(R01MD012579-UT20664DS).

摘　　要：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-β1.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.

关 键 词：Nonalcoholic fatty liver disease(NAFLD) Gelatin methacryloyl(GelMA) PHOTOCROSSLINKING STEATOSIS 

分 类 号：R575.5[医药卫生—消化系统]