【Backgrounds】
Non-alcoholic steatohepatitis (NASH) is developed the fatty liver in alcohol independence and can progress to
cirrhosis or liver cancer in the future. However, there are few therapeutic agents that can improve fibrosis of NASH.
Recently, we established NASH liver organoid model reproducing NASH pathology by using a three-dimensional
organoid culture method.
【Objects】
In this study, the efficacy of 6 types of therapeutic agents currently used in clinical trials on the fibrosis of NASH liver
organoid was evaluated.
【Methods】
7-week-old C57 / BL mice were fed with NASH-induced diet MCD for 12 weeks to prepare advanced fibrosis NASH
mice. Then, the liver was extracted to prepare for organoid culture. The 6 therapeutic agents were treated to NASH
organoids for one week. The morphological changes of organoids and the expression level of fibrosis markers in liver
organoids were evaluated.
【Result and Conclusion】
The morphology of the NASH organoid approached that of the normal liver organoid, and a remarkable
morphological change was observed especially in Farnesoid X Receptor (FXR agonists)treated organoids. Besides, the
expression of collagen I and a-SMA , which are markers related to fibrosis, was significantly decreased in FXR agonists
treated organoids. These results suggest that our established NASH liver organoid model might be useful in the
evaluation of the efficacy of therapeutic drug screening for NASH disease. |
