TY - JOUR
KW - Animals
KW - Disease Models, Animal
KW - Humans
KW - Liver Cirrhosis
KW - Mice
KW - Non-alcoholic Fatty Liver Disease
AU - Tomasz Kostrzewski
AU - Sophie Snow
AU - Anya Lindström Battle
AU - Samantha Peel
AU - Zahida Ahmad
AU - Jayati Basak
AU - Manasa Surakala
AU - Aurelie Bornot
AU - Julia Lindgren
AU - Maria Ryaboshapkina
AU - Maryam Clausen
AU - Daniel Lindén
AU - Christian Maass
AU - Lucy May Young
AU - Adam Corrigan
AU - Lorna Ewart
AU - David Hughes
AB - Non-alcoholic steatohepatitis (NASH) is a common form of chronic liver disease characterised by lipid accumulation, infiltration of immune cells, hepatocellular ballooning, collagen deposition and liver fibrosis. There is a high unmet need to develop treatments for NASH. We have investigated how liver fibrosis and features of advanced clinical disease can be modelled using an in vitro microphysiological system (MPS). The NASH MPS model comprises a co-culture of primary human liver cells, which were cultured in a variety of conditions including+/- excess sugar, fat, exogenous TGFβ or LPS. The transcriptomic, inflammatory and fibrotic phenotype of the model was characterised and compared using a system biology approach to identify conditions that mimic more advanced clinical disease. The transcriptomic profile of the model was shown to closely correlate with the profile of patient samples and the model displayed a quantifiable fibrotic phenotype. The effects of Obeticholic acid and Elafibranor, were evaluated in the model, as wells as the effects of dietary intervention, with all able to significantly reduce inflammatory and fibrosis markers. Overall, we demonstrate how the MPS NASH model can be used to model different aspects of clinical NASH but importantly demonstrate its ability to model advanced disease with a quantifiable fibrosis phenotype.
BT - Communications Biology
DA - 2021-09-15
DO - 10.1038/s42003-021-02616-x
IS - 1
LA - eng
N2 - Non-alcoholic steatohepatitis (NASH) is a common form of chronic liver disease characterised by lipid accumulation, infiltration of immune cells, hepatocellular ballooning, collagen deposition and liver fibrosis. There is a high unmet need to develop treatments for NASH. We have investigated how liver fibrosis and features of advanced clinical disease can be modelled using an in vitro microphysiological system (MPS). The NASH MPS model comprises a co-culture of primary human liver cells, which were cultured in a variety of conditions including+/- excess sugar, fat, exogenous TGFβ or LPS. The transcriptomic, inflammatory and fibrotic phenotype of the model was characterised and compared using a system biology approach to identify conditions that mimic more advanced clinical disease. The transcriptomic profile of the model was shown to closely correlate with the profile of patient samples and the model displayed a quantifiable fibrotic phenotype. The effects of Obeticholic acid and Elafibranor, were evaluated in the model, as wells as the effects of dietary intervention, with all able to significantly reduce inflammatory and fibrosis markers. Overall, we demonstrate how the MPS NASH model can be used to model different aspects of clinical NASH but importantly demonstrate its ability to model advanced disease with a quantifiable fibrosis phenotype.
PY - 2021
EP - 1080
T2 - Communications Biology
TI - Modelling human liver fibrosis in the context of non-alcoholic steatohepatitis using a microphysiological system
VL - 4
SN - 2399-3642
ER -