Biomaterial Database

In Vitro Human Liver Model of Nonalcoholic Steatohepatitis by Coculturing Hepatocytes, Endothelial Cells, and Kupffer Cells. 2019

Ceri-Anne E Suurmond, and Soufian Lasli, and Floor W van den Dolder, and Aly Ung, and Han-Jun Kim, and Praveen Bandaru, and KangJu Lee, and Hyun-Jong Cho, and Samad Ahadian, and Nureddin Ashammakhi, and Mehmet R Dokmeci, and Junmin Lee, and Ali Khademhosseini

Department of Bioengineering, Henry Samueli School of Engineering and Applied Sciences, University of California-Los Angeles, Los Angeles, CA, 90095, USA.

The liver has a complex and unique microenvironment with multiple cell-cell interactions and internal vascular networks. Although nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with multiple phases, no proper model could fully recapitulate the in vivo microenvironment to understand NAFLD progression. Here, an in vitro human liver model of NAFLD by coculturing human hepatocytes, umbilical vein endothelial cells (HUVECs), and Kupffer cells (KCs) into spheroids is presented. Analysis of indirect cross-talk using conditioned media between steatotic spheroids-composed of hepatocellular carcinoma-derived cells (HepG2) and HUVECs-and mouse KCs reveals that the latter can be activated showing increased cell area, elevated production of reactive oxygen species (ROS), and proinflammatory cytokines. Spheroids incorporating human KCs (HKCs) can also be induced into steatotic stage by supplementing fat. Steatotic spheroids with/without HKCs show different levels of steatotic stages through lipid accumulation and ROS production. Steatotic spheroids made from an immortalized hepatic progenitor cell line (HepaRG) compared to those made from HepG2 cells display similar trends of functionality, but elevated levels of proinflammatory cytokines, and improved reversibility of steatosis. The in vitro human liver system proposed makes strides in developing a model to mimic and monitor the progression of NAFLD.

UI	MeSH Term	Description	Entries
D007728	Kupffer Cells	Specialized phagocytic cells of the MONONUCLEAR PHAGOCYTE SYSTEM found on the luminal surface of the hepatic sinusoids. They filter bacteria and small foreign proteins out of the blood and dispose of worn out red blood cells.	Kupffer Cell,Cell, Kupffer,Cells, Kupffer
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D017077	Culture Media, Conditioned	Culture media containing biologically active components obtained from previously cultured cells or tissues that have released into the media substances affecting certain cell functions (e.g., growth, lysis).	Conditioned Culture Media,Conditioned Culture Medium,Conditioned Media,Conditioned Medium,Culture Medium, Conditioned,Media, Conditioned,Medium, Conditioned
D017382	Reactive Oxygen Species	Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.	Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D042783	Endothelial Cells	Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.	Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell
D056945	Hep G2 Cells	A human liver tumor cell line used to study a variety of liver-specific metabolic functions.	Cell Line, Hep G2,Cell Line, Hepatoblastoma G2,Hep G2 Cell Line,HepG2 Cells,Hepatoblastoma G2 Cell Line,Cell, Hep G2,Cell, HepG2,Cells, Hep G2,Cells, HepG2,Hep G2 Cell,HepG2 Cell
D061307	Human Umbilical Vein Endothelial Cells	Endothelial cells that line venous vessels of the UMBILICAL CORD.	Human Umbilical Vein Endothelial Cell,Endothelial Cells, Human Umbilical Vein,HUVEC Cells,Cell, HUVEC,Cells, HUVEC,HUVEC Cell
D022781	Hepatocytes	The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.	Hepatic Cells,Cell, Hepatic,Cells, Hepatic,Hepatic Cell,Hepatocyte
D065626	Non-alcoholic Fatty Liver Disease	Fatty liver finding without excessive ALCOHOL CONSUMPTION.	Fatty Liver, Nonalcoholic,NAFLD,Nonalcoholic Fatty Liver Disease,Nonalcoholic Steatohepatitis,Fatty Livers, Nonalcoholic,Liver, Nonalcoholic Fatty,Livers, Nonalcoholic Fatty,Non alcoholic Fatty Liver Disease,Nonalcoholic Fatty Liver,Nonalcoholic Fatty Livers,Nonalcoholic Steatohepatitides,Steatohepatitides, Nonalcoholic,Steatohepatitis, Nonalcoholic