cb7b00420_si_002.xlsx (719.08 kB)
Ex Vivo Cell-Based Screening Platform for Modulators of Hepatosteatosis
dataset
posted on 2017-06-06, 00:00 authored by Shan Yu, Emily Chen, Lance Sherwood, Mitchell Hull, Ashley K. Woods, Matthew S. TremblayNonalcoholic
fatty liver disease (NAFLD) is the result of the ectopic
accumulation of lipids in hepatic cells and is the early stage of
liver diseases including fibrosis, cirrhosis, and hepatocellular carcinoma.
While some mechanisms of aberrant lipid storage are understood, unbiased
phenotypic drug screening holds the potential to identify new therapeutic
small molecule mechanisms that reverse lipid accumulation in hepatic
cells and prevent disease progression. Immortalized hepatocyte cell
lines are often used as in vitro models of hepatocyte
function, including in the study of lipid accumulation. However, mechanisms
and therapeutic agents studied in these systems suffer from poor translation
to primary cells and animal models of disease. Herein, we report an ex vivo high-throughput screening platform using primary
mouse hepatocytes with a physiologically relevant lipid-laden phenotype
isolated from mice that are administered a choline-methionine deficient
diet. This screening platform using primary diseased hepatocytes may
help to overcome a major hurdle in liver disease drug discovery and
could lead to the development of new therapeutics for hepatosteatosis.