TY - JOUR
KW - disease modeling
KW - Hepatocyte
KW - Lipid
KW - Liver transplant
KW - Steatosis
AU - Elizabeth K. Johnston
AU - Zhou Fang
AU - Alejandro Soto-Gutierrez
AU - C. Burcin Taner
AU - Keith E. Cook
AU - Liu Yang
AU - Rosalyn D. Abbott
AB - Liver transplantation is the key treatment for liver failure, yet organ scarcity, exacerbated by high discard rates of steatotic livers, leads to high waitlist mortality. Preclinical models of steatosis are necessary to understand the pathophysiology of the disease and to develop pharmacological interventions to decrease disease burden and liver discard rate. In this paper, we develop an expedited 3D steatotic organoid model containing primary human hepatocytes and non-parenchymal cells. We present our iterative approach as we transition from 2D to 3D models and from immortalized to primary cells to optimize conditions for the development of a 3D human steatosis model. Both primary cell aggregation and steatosis induction time were reduced from the standard, 5–7 days, to 2 days. Our 3D model incorporates human primary hepatocytes from discarded liver tissues, which have not been used in organoids previously due to their rapid loss of phenotype in culture. After optimizing our steatosis induction media there was a mix of macro- and micro-steatosis in these primary hepatocytes which is consistent with the human pathology. Our approach achieves a model reflective of the liver pathology, preserving cellular phenotypes and viability while exhibiting markers of oxidative stress, a key factor contributing to complications in the transplantation of steatotic livers.
BT - Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
DA - 2025-08-01
DO - 10.1016/j.bbadis.2025.167888
IS - 6
N2 - Liver transplantation is the key treatment for liver failure, yet organ scarcity, exacerbated by high discard rates of steatotic livers, leads to high waitlist mortality. Preclinical models of steatosis are necessary to understand the pathophysiology of the disease and to develop pharmacological interventions to decrease disease burden and liver discard rate. In this paper, we develop an expedited 3D steatotic organoid model containing primary human hepatocytes and non-parenchymal cells. We present our iterative approach as we transition from 2D to 3D models and from immortalized to primary cells to optimize conditions for the development of a 3D human steatosis model. Both primary cell aggregation and steatosis induction time were reduced from the standard, 5–7 days, to 2 days. Our 3D model incorporates human primary hepatocytes from discarded liver tissues, which have not been used in organoids previously due to their rapid loss of phenotype in culture. After optimizing our steatosis induction media there was a mix of macro- and micro-steatosis in these primary hepatocytes which is consistent with the human pathology. Our approach achieves a model reflective of the liver pathology, preserving cellular phenotypes and viability while exhibiting markers of oxidative stress, a key factor contributing to complications in the transplantation of steatotic livers.
PY - 2025
EP - 167888
T2 - Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
TI - Engineering a three-dimensional liver steatosis model
UR - https://www.sciencedirect.com/science/article/pii/S0925443925002364
VL - 1871
Y2 - 2026-07-09
SN - 0925-4439
ER -